evidence_domain,entity_table,evidence_id,canonical_name,modality,target_gene_symbol,disease_context,sense_sequence,antisense_sequence,guide_sequence,passenger_sequence,seed_region,backbone_chemistry,sugar_modification,base_modification,conjugate_delivery,sequence_annotation_status,modification_annotation_status,category,evidence_label,evidence_grade,source_location,source_document_id,source_title,pmid,source_pmcid,doi,source_url,source_license_status,source_reuse_category,curation_basis,raw_quote_included,is_observed_experimental,is_computational_prediction,audit_validation_status,curator_decision,curator_id,audit_note,audited_at
toxicity,toxicity_endpoint,1,phosphorothioate ASO panel from PMID 41760661,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,genotoxicity,DNA damage response,A,Results > ASO treatment cause activation of DNA repair enzymes and these proteins are enriched in ASO-seeded PS bodies; paragraph 15,1002,Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides.,41760661,PMC12954066,10.1038/s41467-026-69980-2,https://pubmed.ncbi.nlm.nih.gov/41760661/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Notably, these condensates become enzymatically active and erroneously elicit the DNA damage response in the absence of DNA damage, activating cell cycle checkpoints, disturbing endogenous repair and causing accumulation of toxic DNA lesions.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,2,tool ASO safety panel from PMID 41918821,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Tool ASO safety profile characterization in vitro and in vivo; paragraph 32,1035,Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach.,41918821,PMC13034028,10.1093/narmme/ugag016,https://pubmed.ncbi.nlm.nih.gov/41918821/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Safety characterization is based on in vitro, in vivo, and clinical data from literature and an in-house study where ALT levels were measured in an acute tolerability study in male BALB/c mice administered with 150 mg/kg ASO by subcutaneous injection.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,4,5?-CP-modified PS-ASO panel from PMID 41467114,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Results > Gap modification of 5′-CP mitigates cytotoxicity and in vivo neurotoxicity across various PS-ASOs; paragraph 25,1028,Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications.,41467114,PMC12744863,10.1016/j.omtn.2025.102692,https://pubmed.ncbi.nlm.nih.gov/41467114/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"ASO2 and ASO3 caused a severe reduction in body weight, whereas ASO1 and ASO4 also induced a significant decrease (Figure S3).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,5,BND6482,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Liver and kidney toxicity assessment of BND6482; paragraph 61,1780,IGF1R-targeted delivery of a bridged nucleic acid oligonucleotide-peptide conjugate for microRNA-21 inhibition in triple-negative breast cancer.,41480638,PMC12754785,10.1093/narcan/zcaf053,https://pubmed.ncbi.nlm.nih.gov/41480638/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Compared to the vehicle and scrambled control groups, BND6482-treated mice showed no significant alterations in serum markers indicative of hepatotoxicity (Fig. 10A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,6,L2-Htt,siRNA,HTT,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,Results > Safety assessments reveal L2-Htt is well tolerated in aged mice; paragraph 43,1782,Evaluating the effects of aging on biodistribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.,41446212,PMC12724171,10.64898/2025.12.17.693452,https://pubmed.ncbi.nlm.nih.gov/41446212/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Collectively, these data demonstrate that L2-siRNA is well tolerated in aged mice, with no evidence of systemic toxicity, neuroinflammation, or organ dysfunction.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,7,TP-siRC@tHyNPs (CYP3A4-siRNA),siRNA,CYP3A4,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,C,RESULTS > Anti-PMM effect of TP-siRC@tHyNPs in vivo; paragraph 30,1822,Engineering hybrid nanoparticles for targeted codelivery of triptolide and CYP3A4-siRNA against pulmonary metastatic melanoma.,40700483,PMC12285696,10.1126/sciadv.adv6990,https://pubmed.ncbi.nlm.nih.gov/40700483/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In contrast, mice treated with TP-siRC@tHyNPs maintained stable hematological and biochemical indices throughout the 28-day administration period.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,8,anti-miR-21-SNA,ASO,MIR21,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Anti–miR-21-SNA Treatment Inhibits Kidney Cyst Growth; paragraph 32,1846,Ameliorative Effect of an Anti-MicroRNA-21 Oligonucleotide on Animal and Human Models of Cystic Kidney Disease.,40178922,PMC12233840,10.34067/KID.0000000771,https://pubmed.ncbi.nlm.nih.gov/40178922/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,blood urea nitrogen levels without inducing hepatotoxicity,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,9,LEM-S401,siRNA,CTGF,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,Results > Safety and Tolerability; paragraph 24,2285,"A First-In-Human Phase 1 Study to Evaluate the Safety and Tolerability of LEM-S401, a Novel siRNA-DegradaBALL Drug Targeting CTGF in Healthy Adults.",40160160,PMC11955805,10.1111/cts.70207,https://pubmed.ncbi.nlm.nih.gov/40160160/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,injection site reactions including pain and erythema,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,10,hypoxanthine-substituted LNA-gapmer ASO1 panel from PMID 41928909,ASO,Mapt,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Result > Nucleobase-dependent effects of hypoxanthine substitution on in vivo CNS toxicity; Fig. 3 caption,1413,Guanine base modifications in antisense oligonucleotides mitigate acute central nervous system toxicity.,41928909,PMC13040562,10.1039/d5cb00316d,https://pubmed.ncbi.nlm.nih.gov/41928909/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"We next evaluated the cytotoxicity of ASO1 and ASO2 as well as the effect of hypoxanthine substitution, Neuro-2a mouse neuroblastoma cells were transfected with ASOs, and LDH release together with cell viability was measured 48 h later.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,11,nebulized siIL-1beta.2 from PMID 41898774,siRNA,IL1B,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,2. Results > 2.6. Knockdown of Endogenously Expressed IL-1β by Nebulized siRNA; paragraph 27,3211,Functional siRNA Delivery via Jet Nebulization: Proof-of-Concept IL-1ß Silencing in Macrophage-like THP-1 Cells.,41898774,PMC13026121,10.3390/ijms27062915,https://pubmed.ncbi.nlm.nih.gov/41898774/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,exhibited cell viability >95% (Figure 1A),2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,12,RGLS4326 anti-miR-17 ASO,ASO,MIR17,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Results > CNS toxicity after RGLS4326 treatment in nonclinical toxicity studies; paragraph 7,1410,The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.,41315228,PMC12663328,10.1038/s41467-025-65799-5,https://pubmed.ncbi.nlm.nih.gov/41315228/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"During development of RGLS4326, unexpected CNS toxicity (characterized by abnormal gait, lateral recumbency, ataxia, and lethargy) and mortality (including unscheduled euthanasia due to moribundity) were observed in a chronic toxicity study in mice (Supplementary Table 1).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,13,SNS812,siRNA,SARS-CoV-2 RdRP,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,Results > Primary Efficacy: Safety; paragraph 27,2286,"Pharmacokinetics and Safety Profile of SNS812, a First in Human Fully Modified siRNA Targeting Wide-Spectrum SARS-CoV-2, in Healthy Subjects.",40116355,PMC11926758,10.1111/cts.70202,https://pubmed.ncbi.nlm.nih.gov/40116355/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,TEAEs caused discontinuation or deaths were observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,15,siSNCA PEI/PPI nanoparticle panel from PMID 40978531,siRNA,SNCA,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,Results > PEI/PPI-based nanoparticles reveal low cytotoxic potential and polymer-dependently knock down SNCA mRNA in vitro; paragraph 6,3500,Nose-to-brain siRNA delivery by PEI/PPI-based nanoparticles reduces α-synuclein expression in a Parkinson's disease mouse model.,40978531,PMC12447568,10.1016/j.omtn.2025.102671,https://pubmed.ncbi.nlm.nih.gov/40978531/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,indicating the absence of acute cytotoxicity,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,16,JNJ-3989/JNJ-73763989 GalNAc-siRNA regimen from PMID 40919077,siRNA,HBV,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,Results > Safety; paragraph 22,3517,Peginterferon-alpha-2a add-on to treatment with siRNA JNJ-73763989 in virologically suppressed chronic hepatitis B: The phase II PENGUIN study.,40919077,PMC12409438,10.1016/j.jhepr.2025.101516,https://pubmed.ncbi.nlm.nih.gov/40919077/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Safety and tolerability of study drugs and procedures were evaluated via assessments of adverse events (AEs), including serious AEs (SAEs), physical examination, and laboratory abnormalities, including changes in ALT throughout the study.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,17,scFv-MML@LPCAT1si from PMID 40898177,siRNA,LPCAT1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > In vivo safety access; paragraph 30,3529,Biomimetic nanoparticles coated with ScFv-modified macrophage membranes for siRNA delivery to relieve brain metastases of lung cancer.,40898177,PMC12406594,10.1186/s12896-025-01000-5,https://pubmed.ncbi.nlm.nih.gov/40898177/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Furthermore, blood tests for hepatic function indicators (ALT and AST levels) and renal function indicators (creatinine and BUN levels) revealed no significant systemic toxicity across all groups (Fig. 6B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,18,Cet/siFAK@ZIF-8@TCM from PMID 40735032,siRNA,PTK2,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,"Results > In vitro evaluation of cytotoxicity, homologous targeting, and immune escape; paragraph 32",3574,pH-responsive biomimetic zeolitic imidazolate framework-based nanoparticles for co-delivery of cetuximab and siRNA in synergistic therapy of laryngeal squamous cell carcinoma.,40735032,PMC12305587,10.1016/j.jpha.2025.101203,https://pubmed.ncbi.nlm.nih.gov/40735032/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No differences in the indicators of liver and kidney function were observed among the control, Cet@ZIF-8@TCM, siFAK@ZIF-8@TCM, and Cet/siFAK@ZIF-8@TCM groups (Fig. 7A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,19,EM/siKEAP1@Fe-MOF@HA from PMID 40688667,siRNA,KEAP1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > Assessment of biosafety in vivo; paragraph 42,3590,Hyaluronic acid-anchored nanoparticles co-delivering emodin and siRNA confers protection against rheumatoid arthritis via macrophage polarization.,40688667,PMC12274865,10.1016/j.mtbio.2025.102074,https://pubmed.ncbi.nlm.nih.gov/40688667/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Detection for serum levels of ALT, AST, BUN, and Cre also indicated no significant differences in liver and kidney functions among the groups (Fig. 8C).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,20,DCA-siRNADUX4/DU01 from PMID 40673060,siRNA,DUX4,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,transcriptome toxicity,C,Results > Transcriptomic analysis of FSHD myotubes after siRNADUX4 treatment; paragraph 9,3598,A systemically deliverable lipid-conjugated siRNA targeting DUX4 as an facioscapulohumeral muscular dystrophy therapeutic.,40673060,PMC12264612,10.1016/j.omtm.2025.101513,https://pubmed.ncbi.nlm.nih.gov/40673060/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40673060; weak/generic or abstract-limited support for general safety/transcriptome toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,21,hEV@FAP-siTGFbeta1 from PMID 40046817,siRNA,TGFB1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > In vivo Safety of hEV@FAP-siTGFβ1; paragraph 42,3740,Injured Cardiac Tissue-Targeted Delivery of TGFβ1 siRNA by FAP Aptamer-Functionalized Extracellular Vesicles Promotes Cardiac Repair.,40046817,PMC11881639,10.2147/IJN.S497428,https://pubmed.ncbi.nlm.nih.gov/40046817/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Histological examination of major organs, including the heart, liver, spleen, lung, and kidneys, revealed no noticeable changes or damage in H&E-stained sections following intravenous injection of each EV sample (Figure 6A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,22,siAURKA-loaded milk extracellular vesicles from PMID 40896585,siRNA,AURKA,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Results > Safety and immune-response of siRNA-loaded mEVs; paragraph 15,8490,RNAi delivery mediated by milk extracellular vesicles in colon cancer.,40896585,PMC12396431,10.1016/j.omtn.2025.102644,https://pubmed.ncbi.nlm.nih.gov/40896585/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40896585; weak/generic or abstract-limited support for immunotoxicity/immune activation.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,23,BSCgal gold-siRNA supracluster from PMID 39448881,siRNA,LGALS1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > In vivo clearance and traceable delivery of supraclusters; paragraph 9,12426,Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors.,39448881,PMC12018592manuscript-id: NIHMS2046510,10.1038/s41587-024-02448-0,https://pubmed.ncbi.nlm.nih.gov/39448881/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Moreover, ELISA indicated that GSC and BSCgal treatments did not trigger an elevation of inflammatory markers, such as C-reactive protein, procalcitonin and interleukin-6, in mouse serum, further verifying the excellent biocompatibility of supraclusters (Supplementary Fig. 16).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,24,G-clamp/BNAP-AEO modified Malat1 ASO panel from PMID 38978695,ASO,MALAT1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Results > G-clamp modification in ASO targeting Malat1 RNA mitigates acute CNS toxicity of ASO; paragraph 11,1110,"Favorable efficacy and reduced acute neurotoxicity by antisense oligonucleotides with 2',4'-BNA/LNA with 9-(aminoethoxy)phenoxazine.",38978695,PMC11229412,10.1016/j.omtn.2024.102161,https://pubmed.ncbi.nlm.nih.gov/38978695/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The 20-mer ASO including only DNA (ASO1) and the 20-mer ASO with two LNAs (ASO2) induced high acute CNS toxicity in the acute toxicity scoring system compared with PBS (Video S1), and this toxicity persisted for 4 h after ICV administration.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,25,aCSF+-formulated CNS ASO/di-siRNA panel from PMID 39554992,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Results > Using aCSF+ reduces the acute neurotoxicity of CNS-administered ASOs; paragraph 26,1115,Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca(2+) and Mg(2+) in the formulation.,39554992,PMC11567125,10.1016/j.omtn.2024.102359,https://pubmed.ncbi.nlm.nih.gov/39554992/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,decreased the severity of adverse events in a dose-dependent manner,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,26,pVEC-ASO panel from PMID 38391508,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,3. Results > 3.3. Cell Growth Inhibition by Antisense Oligonucleotides; paragraph 21,1417,General and Specific Cytotoxicity of Chimeric Antisense Oligonucleotides in Bacterial Cells and Human Cell Lines.,38391508,PMC10885958,10.3390/antibiotics13020122,https://pubmed.ncbi.nlm.nih.gov/38391508/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The final MTT assays were performed in non-tumor human fibroblast cell line Lep3 (Figure 8). The experiment was conducted to measure the cell toxicity and cell proliferation of all the designed pVEC-ASOs.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,27,LNP-siTGFbetaRI from PMID 39264964,siRNA,TGFBR1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,3. Results > 3.7. In vivo toxicity of LNP-siTGFβRI; paragraph 36,1886,Development of a Lipid-encapsulated TGFβRI-siRNA Drug for Liver Fibrosis Induced by Schistosoma mansoni.,39264964,PMC11421824,10.1371/journal.pntd.0012502,https://pubmed.ncbi.nlm.nih.gov/39264964/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,no systemic toxicity was observed in major organs.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,28,CT102,ASO,IGF1R,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,Results > Participants in phase I clinical trial; paragraph 55,2600,Preclinical and phase I studies of an antisense oligonucleotide drug targeting IGF-1R in liver cancer.,38573183,PMC11534120,10.2217/fon-2023-0872,https://pubmed.ncbi.nlm.nih.gov/38573183/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,CT102 showed safety and tolerability in participants with advanced primary liver cancer. The maximum tolerated dose of a single dose of CT102 was 3.96 mg/kg.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,30,GxS5/siRNA polyplexes from PMID 39263399,siRNA,tdTomato,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,Results > Efficacy as siRNA carrier for RNA interference; paragraph 52,3851,Efficient siRNA delivery to murine melanoma cells via a novel genipin-based nano-polymer.,39263399,PMC11386170,10.1039/d4na00363b,https://pubmed.ncbi.nlm.nih.gov/39263399/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 39263399; weak/generic or abstract-limited support for general safety/cytotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,31,GBE-PLL/H2O-PLL solid lipid nanoparticle siRNA carriers from PMID 39684010,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,apoptosis/cytotoxicity,C,3. Results > 3.6. Caspase 3/7 Activity; paragraph 35,12064,Bio-Inspired Polymeric Solid Lipid Nanoparticles for siRNA Delivery: Cytotoxicity and Cellular Uptake In Vitro.,39684010,PMC11644305,10.3390/polym16233265,https://pubmed.ncbi.nlm.nih.gov/39684010/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The GBE-PLL-SLNPs had an average size of 93.2 nm and demonstrated enhanced binding and protection of the siRNA from enzyme digestion, with minimal cytotoxicity in HEK293 (<10%) and SH-SY5Y cells (<15%).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,32,P-E/S Lip PD-L1 siRNA nanovesicle from PMID 39068444,siRNA,CD274,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,Results > Synthesis and functional validation of P-E/S lip in vitro; paragraph 26,12122,PD-L1 siRNA hitched polyethyleneimine-elastase constituting nanovesicle induces tumor immunogenicity and PD-L1 silencing for synergistic antitumor immunotherapy.,39068444,PMC11282766,10.1186/s12951-024-02700-4,https://pubmed.ncbi.nlm.nih.gov/39068444/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Results indicated that mouse body weights were generally stable during the dosing period, and histologic analysis data showed no apparent damage or lesions in major organs (Fig. S8c-S8d).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,33,SWNT-PL-PEG-S-S-siLUC conjugate from PMID 39627280,siRNA,LUC,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,acute systemic safety,C,Results > Significant knock-down efficacy using SWNT-PL-PEG-S-S-siRNA conjugate in a mouse xenograft model; paragraph 19,12435,Polyethylene glycol-phospholipid functionalized single-walled carbon nanotubes for enhanced siRNA systemic delivery.,39627280,PMC11615393,10.1038/s41598-024-80646-1,https://pubmed.ncbi.nlm.nih.gov/39627280/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No significant body weight loss was observed following administration of SWNT-PL-PEG-S-S-siLUC to the HCT-116 xenograft in BALB/C nude mice.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,34,OligoA-11/Skeen-11 phosphorothioate oligonucleotide panel from PMID 37185731,ASO,G6PD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic; renal,hepatic and renal toxicity,B,2. Results; paragraph 20,1138,Inhibitory Effect of Phosphorothioate Oligonucleotide Complementary to G6PD mRNA on Murine Melanoma.,37185731,PMC10137061,10.3390/cimb45040207,https://pubmed.ncbi.nlm.nih.gov/37185731/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The introduction of phosphorothioate oligonucleotides does not have significant additional destructive effects on the liver and kidneys of animals.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,35,miR-125a-5p agomir from PMID 36632217,miRNA agomir,MIR125A,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cardiac and systemic safety,B,Results > Myocardial I/R swine receiving miR-125a-5p agomir show no alterations in arrhythmic occurrences and serum chemistries; paragraph 23,1960,Therapeutic delivery of microRNA-125a-5p oligonucleotides improves recovery from myocardial ischemia/reperfusion injury in mice and swine.,36632217,PMC9830430,10.7150/thno.73568,https://pubmed.ncbi.nlm.nih.gov/36632217/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Myocardial I/R swine receiving miR-125a-5p agomir show no alterations in arrhythmic occurrences and serum chemistries,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,36,CLCN7G215R-siRNA-SiS12 formulation from PMID 37680985,siRNA,CLCN7,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > Safety analysis; paragraph 31,2657,Novel hybrid silicon-lipid nanoparticles deliver a siRNA to cure autosomal dominant osteopetrosis in mice. Implications for gene therapy in humans.,37680985,PMC10480457,10.1016/j.omtn.2023.08.020,https://pubmed.ncbi.nlm.nih.gov/37680985/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,serological disease biomarkers of liver (alanine aminotransferase and alkaline phosphatase) (Figure 5I) and kidney (urea) (Figure 5K) were unchanged in all treated ADO2 mice compared with the WT controls.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,37,RBCEV-delivered siMstn and siMlycd from PMID 37016578,siRNA,MSTN; MLYCD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune and systemic safety,B,Results > Intramuscular delivery of siRNAs using RBCEVs is non-toxic and non-inflammatory; paragraph 22,4022,Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia.,37016578,PMC10188904,10.1016/j.ymthe.2023.03.036,https://pubmed.ncbi.nlm.nih.gov/37016578/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"repeated intramuscular administrations with Mstn siRNA or Mlycd siRNA loaded into red blood cell extracellular vesicles result in inhibition of Mstn or Mlycd gene expression, increased muscle growth, and prevention of cachexia in cancer-bearing mice without considerably systemic toxicity and inflammation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,38,ASO1-ASO3 modified ASO panel from PMID 36700050,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,A,Results > Effect of ASO oligonucleotide sequence and modifications on neurotoxicity; paragraph 16,12067,Change of intracellular calcium level causes acute neurotoxicity by antisense oligonucleotides via CSF route.,36700050,PMC9843489,10.1016/j.omtn.2022.12.010,https://pubmed.ncbi.nlm.nih.gov/36700050/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The toxic ASOs were found to reduce consciousness and locomotor function in mice in a dose-dependent manner.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,39,TS1-ASO nucleobase modification panel from PMID 35801870,ASO,TTR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > Identification of potential nucleobase modifications that reduce LNA gapmer hepatotoxicity; Figure 2. caption,1409,Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.,35801870,PMC9303313,10.1093/nar/gkac562,https://pubmed.ncbi.nlm.nih.gov/35801870/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,reduced serum AST/ALT levels by 0.3,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,40,ESC+ GalNAc-siRNA D1/D4/D6/D9 panel from PMID 35736224,siRNA,TTR; HAO1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > GNA improves the therapeutic index in rats; paragraph 33,1411,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization.,35736224,PMC9262600,10.1093/nar/gkac539,https://pubmed.ncbi.nlm.nih.gov/35736224/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The increased levels of ALT, AST and GLDH observed in animals treated with the parent D1 were completely normalized with D16, which closely mimicked that of the saline control (Figure 4D).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,41,DLin-MC3-DMA-conjugated siRNA panel from PMID 35917865,siRNA,HTT; PPIB,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,transcriptome toxicity,B,Results > DLin-MC3-DMA conjugate induces non-specific modulation of gene expression in several tissues; paragraph 35,1427,Engineered ionizable lipid siRNA conjugates enhance endosomal escape but induce toxicity in vivo.,35917865,PMC10281028manuscript-id: NIHMS1882446,10.1016/j.jconrel.2022.07.041,https://pubmed.ncbi.nlm.nih.gov/35917865/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 35917865; weak/generic or abstract-limited support for general safety/transcriptome toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,42,siLuc-ALC-0315 LNP from PMID 35642083,siRNA,LUC,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > A high intravenous dose of ALC-0315 LNPs increases some markers of liver toxicity.; paragraph 21,1979,Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells.,35642083,PMC9621687manuscript-id: NIHMS1814479,10.1021/acs.molpharmaceut.2c00033,https://pubmed.ncbi.nlm.nih.gov/35642083/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Mice treated with siLuc-ALC-0315 had significantly higher serum levels of ALT and bile acids,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,43,PEG-SSN/siRNA nanoparticle formulation from PMID 36412852,siRNA,EGFR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity and hemolysis,C,3. Results > 3.8. Biocompatibility Assay; paragraph 41,2305,PEGylated Strontium Sulfite Nanoparticles with Spontaneously Formed Surface-Embedded Protein Corona Restrict Off-Target Distribution and Accelerate Breast Tumour-Selective Delivery of siRNA.,36412852,PMC9680366,10.3390/jfb13040211,https://pubmed.ncbi.nlm.nih.gov/36412852/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"As shown in Figure 8B, no noticeable hemolysis was found for SSNs and PEG-SSNs compared to the control group.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,45,GalNAc-G-quadruplex oligonucleotide panel from PMID 35745067,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,2. Results > 2.4. Toxicity Assays; paragraph 17,4073,Properties of Parallel Tetramolecular G-Quadruplex Carrying N-Acetylgalactosamine as Potential Enhancer for Oligonucleotide Delivery to Hepatocytes.,35745067,PMC9228010,10.3390/molecules27123944,https://pubmed.ncbi.nlm.nih.gov/35745067/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Prior the evaluation of internalization and antisense inhibition of luciferase, we evaluate the potential toxicity of GalNAc-oligonucleotides by using MTT assay at 60 nM, 120 nM and 300 nM oligonucleotide concentration after 24 h.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,46,A10-3.2/siCAT-1/3WJ nanodroplets from PMID 35037525,siRNA,SLC7A1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,Results > In vitro bio-safety of NDs; paragraph 33,4096,Utilizing RNA nanotechnology to construct negatively charged and ultrasound-responsive nanodroplets for targeted delivery of siRNA.,35037525,PMC8765274,10.1080/10717544.2022.2026532,https://pubmed.ncbi.nlm.nih.gov/35037525/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"At used concentration for cell experiments in this study (<0.2 mg/mL), the cell survival rate was all above 95%, which indicates that these NDs have high bio-safety.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,47,CYP3A5 PMO/PSO panel from PMID 33633318,ASO,CYP3A5,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results; paragraph 14,1471,Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease.,33633318,PMC7907328,10.1038/s41598-021-84194-w,https://pubmed.ncbi.nlm.nih.gov/33633318/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Efficiency of restoration of CYP3A5 activity by the 3A5*3 PMO was donor-dependent (Donor 3; See Supplemental Table 1), and was not related to cellular toxicity, as PMO treatments did not alter normal PTEC morphology (see Supplemental Fig. 9).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,48,HsPCSK9-1811-LNA/GalNAc ASO panel from PMID 34760338,ASO,PCSK9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal; hepatic,renal and hepatic safety,A,Results > Evaluating the safety of the GalNAc conjugate in rat; paragraph 15,1632,Drug discovery and development scheme for liver-targeting bridged nucleic acid antisense oligonucleotides.,34760338,PMC8560717,10.1016/j.omtn.2021.10.008,https://pubmed.ncbi.nlm.nih.gov/34760338/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Histopathological examination revealed mild injury with degeneration, karyomegaly, single-cell necrosis, and vacuolation in proximal tubules in both animals dosed at 30 mg/kg.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,49,LNA-ASO renal histopathology panel from PMID 34629736,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal histopathology,C,article body; paragraph 10,1636,Karnovsky's fixative prevents artifacts appearing as vacuolation derived from tissue processing in kidneys treated with antisense oligonucleotide.,34629736,PMC8484925,10.1293/tox.2021-0007,https://pubmed.ncbi.nlm.nih.gov/34629736/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Microscopically, vacuoles and basophilic granules in the proximal tubules were observed in the kidneys fixed with NBF.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,50,LUNAR-REPU910 siRNA from PMID 33738134,siRNA,AR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,neurodevelopmental safety,C,Results > Selective suppression of polyQ-expanded AR by i.c.v.-injected LUNAR-REPU910 siRNA; paragraph 12,1646,Selective suppression of polyglutamine-expanded protein by lipid nanoparticle-delivered siRNA targeting CAG expansions in the mouse CNS.,33738134,PMC7937577,10.1016/j.omtn.2021.02.007,https://pubmed.ncbi.nlm.nih.gov/33738134/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"I.c.v. injection of maximum dose (1,800 ng) of REPU910 had no adverse effect on mouse phenotypes, including motor function, growth, and survival.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,51,LNPssPalmO-Phe-ASOap/ASOgr from PMID 33924589,ASO,APOB; NR3C1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,3. Results > 3.3. Application for the Delivery of ASO > 3.3.2. Comparison of Hepatotoxicity between ASO and LNPssPalmO-Phe–ASO; paragraph 24,1999,Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material.,33924589,PMC8070490,10.3390/pharmaceutics13040544,https://pubmed.ncbi.nlm.nih.gov/33924589/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,LNPssPalmO-Phe–ASOap induced severe hepatotoxicity when injected at a dose of 0.37 mg/kg,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,52,2'-O-methoxyethyl chimeric ASO tolerability dataset from PMID 34242101,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,tolerability events,C,Results > Incidence and percentage of doses leading to adverse events; paragraph 22,2741,"Improvements in the Tolerability Profile of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in Parallel with Advances in Design, Screening, and Other Methods.",34242101,PMC8713270,10.1089/nat.2020.0917,https://pubmed.ncbi.nlm.nih.gov/34242101/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The incidence and mean percentage of doses leading to ISR, LCRIS, and FLR events were significantly lower in the test group, compared with mipomersen (Table 3 and Fig. 2).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,53,dual-RGD/EGFR siRNA protein nanocarrier from PMID 34959463,siRNA,EGFR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,C,3. Results > 3.9. Toxicity Assessment; paragraph 31,4106,Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery.,34959463,PMC8703291,10.3390/pharmaceutics13122182,https://pubmed.ncbi.nlm.nih.gov/34959463/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,H&E staining revealed that there was no discernible abnormality observed in dual-RGD protein-treated groups compared with the saline-treated control.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,54,PMO-P6 conjugate from PMID 34841414,ASO,DMD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > In Vivo Studies; paragraph 30,4112,Deep Learning Enables Discovery of a Short Nuclear Targeting Peptide for Efficient Delivery of Antisense Oligomers.,34841414,PMC8611673,10.1021/jacsau.1c00327,https://pubmed.ncbi.nlm.nih.gov/34841414/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No changes were found in the levels of these three renal function markers 7 days post-treatment which indicates that PMO–P6 is not toxic to the kidney at the doses tested,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,55,PM1(GT/siMMP-9) hydrogel from PMID 33952251,siRNA,MMP9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,local and systemic safety,B,Results > In vivo biocompatibility of PM1(GT/siMMP-910) hydrogel; paragraph 60,4145,Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing.,33952251,PMC8097905,10.1186/s12951-021-00869-6,https://pubmed.ncbi.nlm.nih.gov/33952251/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Serum AST, ALT, Cr and BUN levels indicated no significant differences in all treated groups compared to negative control (PBS treated group) (Additional file 1: Table S5).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,56,stereocontrolled cEt gapmer ASO panel from PMID 31980820,ASO,MALAT1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,B,RESULTS > Biological evaluation of fully Rp and Sp gap modified ASOs; paragraph 18,1423,Understanding the effect of controlling phosphorothioate chirality in the DNA gap on the potency and safety of gapmer antisense oligonucleotides.,31980820,PMC7038945,10.1093/nar/gkaa031,https://pubmed.ncbi.nlm.nih.gov/31980820/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,ASO FR7S-G showed the best potency but was extremely toxic at all doses which made it difficult to calculate an ED50 for CXCl12 mRNA reduction (Figure 3).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,57,306-O12B-3 ASO/LNP formulation from PMID 32160706,ASO,GFP,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytotoxicity,C,Results > Screening the Bioreducible Lipids for ASO Delivery In Vitro; paragraph 16,1493,Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo.,32160706,PMC7036716,10.1016/j.omtn.2020.01.018,https://pubmed.ncbi.nlm.nih.gov/32160706/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The LNPs comprising 306-O12B-3 were well tolerated at all dose levels and observed no clinically significant change in mouse behavior, spleen size, and key hepatotoxic or nephrotoxic parameters (Table 1).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,58,H51(+67)W tcDNA-ASO from PMID 31881528,ASO,DMD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic; renal,hepatic and renal safety,A,Results > Safety Biomarkers at the End of H51(+67)W Treatment; paragraph 14,2225,Identifying and Avoiding tcDNA-ASO Sequence-Specific Toxicity for the Development of DMD Exon 51 Skipping Therapy.,31881528,PMC7063478,10.1016/j.omtn.2019.11.020,https://pubmed.ncbi.nlm.nih.gov/31881528/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In vivo and in vitro assays revealed complement activation, prolonged coagulation times, and platelet activation, correlating with the observed toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,59,GalNAc AON-B/D/E panel from PMID 30583097,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > GalNAc Conjugation Masked the In Vivo Nephrotoxicity Potential of AON Drug Candidates; paragraph 7,2059,GalNAc Conjugation Attenuates the Cytotoxicity of Antisense Oligonucleotide Drugs in Renal Tubular Cells.,30583097,PMC6305803,10.1016/j.omtn.2018.11.005,https://pubmed.ncbi.nlm.nih.gov/30583097/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Indeed, mild histopathological abnormalities were observed in the renal cortex of one rat treated with GalNac AON-B in a 2-week study (Figure 2A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,60,GalNAc-siRNA hepatotoxicity panel with REVERSIR from PMID 29459660,siRNA,HAO1; TTR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Blocking siRNA-loaded RISC activity mitigates hepatotoxicity; paragraph 12,2058,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity.,29459660,PMC5818625,10.1038/s41467-018-02989-4,https://pubmed.ncbi.nlm.nih.gov/29459660/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In the rat, hepatotoxic siRNAs (siRNA-1 shown here) had hepatocellular degeneration (bracketed area), increased sinusoidal cells due to Kupffer cell hyperplasia and/or leukocyte infiltration (#), single cell necrosis (*), increased mitoses (^), and hepatocellular vacuolation (arrow).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,61,236-LNA-ASO hepatotoxicity screening panel from PMID 29499955,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Apoptosis Induction by Hepatotoxic LNA-ASOs In Vitro Is RNase H1 Dependent; paragraph 8,2319,A Sensitive In Vitro Approach to Assess the Hybridization-Dependent Toxic Potential of High Affinity Gapmer Oligonucleotides.,29499955,PMC5725219,10.1016/j.omtn.2017.11.004,https://pubmed.ncbi.nlm.nih.gov/29499955/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"This in vitro assay accurately reflects in vivo findings and relates hepatotoxicity to RNase H1 activity, off-target RNA downregulation, and LNA-ASO-binding affinity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,62,nephrotoxic AON A/B/C panel from PMID 28325303,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > Identification of Extracellular EGF as an In Vitro Marker of AON-Induced Tubulotoxicity; paragraph 9,2106,Inhibition of EGF Uptake by Nephrotoxic Antisense Drugs In Vitro and Implications for Preclinical Safety Profiling.,28325303,PMC5363415,10.1016/j.omtn.2016.11.006,https://pubmed.ncbi.nlm.nih.gov/28325303/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"elevation of EGF in the supernatant of PTEC-TERT1 is most likely a result of dysfunctional uptake by EGFR rather than a stimulated production and secretion of EGF. We verified this hypothesis by confirming that PTEC-TERT1 efficiently deplete EGF from the medium within 72 hr (Figure 3A), express EGFR, and do not express detectable level of EGF even after exposure to AONs (Figure 3B). In addition, we compared the EGF profile of AON-treated PTEC-TERT1 in the presence and absence of extracellular EGF in the medium and observed that accumulation of soluble EGF occurred only when the medium was supplemented with EGF (Figure 3C). To visualize the capacity of AON-treated cells to internalize extracellular EGF, PTEC-TERT1 were exposed to AONs for 6 days, incubated overnight without EGF, and incubated 10 min at 37°C with a fluorescently labeled EGF (EGF-488) in AON-free medium (scheme Figure 3D). EGF uptake and intracellular accumulation was visible in the form of green foci in vehicle-treated cells and was fully blocked by simultaneous incubation with cetuximab, a monoclonal antibody that blocks EGF binding to EGFR19 (Figure 3D, upper panels). AON-A-treated cells normally accumulated EGF-488, whereas pre-exposure to toxic AON-D, AON-B, AON-C, and AON-E significantly reduced the number of EGF-488 foci (Figure 3D, lower panels; see Figure S6 for quantification). The decreased number of intracellular EGF foci together with the accumulation of EGF in the medium suggest that EGF uptake is dysfunctional in toxic AON-treated PTEC-TERT1 cells. To determine whether AON-mediated alterations in EGF transport are restricted to a renal epithelial cell model, we replaced PTEC-TERT1 with human primary hepatocytes, a cell model that is competent for gymnotic uptake of AONs,20 expresses EGFR but is not dependent on EGF for in vitro proliferation and survival (Figure S7). Human hepatocytes cultivated and seeded in a conventional EGF-free medium were exposed to safe and tubulotoxic AONs along with 10 ng/mL of EGF. Intracellular ATP and extracellular EGF were measured concomitantly after 3 days of AON exposure. AON-B and AON-C showed significantly elevated EGF levels whereas AONs D and E had minimal changes in EGF (Figure 3E). AON-C did not lead to a substantial reduction in intracellular ATP in human hepatocytes despite strong EGF elevation, thus uncoupling the two readouts and implying that reduced EGF uptake is not solely caused by a general cellular deterioration. In addition, we exposed the ARPE-19 retinal pigment epithelial cell line to AONs in cell medium supplemented with EGF. We observed an accumulation of EGF in the supernatant of AON-C-treated ARPE-19 associated with a decrease in intracellular ATP (Figure 3F). Interestingly, ARPE-19 did not show signs of cytotoxicity in response to AON-B and AON-E, thus highlighting the importance of choosing the most appropriate and responsive cell model to fully capture the toxicity potential of AONs with correlation to histopathology findings. Blockage of EGF-Induced and EGFR-Dependent Cellular Activity by Toxic AONs Following the finding that tubulotoxic AONs impair EGF uptake, we assessed whether tubulotoxicity is correlated with the amount of extracellular EGF in the medium. PTEC-TERT1 were grown until confluence in regular EGF-containing medium (10 ng/mL) and measurements of intracellular ATP and extracellular EGF accumulation were performed after simultaneous incubation with AON along with 0, 1, 3, 10, 30, or 100 ng/mL of EGF. This experiment showed that regulation of intracellular ATP levels in confluent, non-dividing PTEC-TERT1 is dependent on EGF concentration (Figure 4A). Remarkably, the toxicity profile of AONs D, B, and C was no longer observed at 0 and 1 ng/mL of EGF, and noticeable differences between innocuous and toxic AONs required 10 ng/mL or higher concentrations of EGF (Figure 4A). Importantly, AON target reduction was not affected by the presence or absence of EGF (Figure 4B). These data suggest that toxic AONs may block EGF-dependent cellular energy production. To further investigate this hypothesis, we monitored the effect of AONs after inhibition of EGFR signaling with Cetuximab. Similar to toxic AONs, cetuximab alone reduced EGF-induced intracellular ATP (Figure 4C). The combination of AONs and cetuximab had little synergistic or additional effects on ATP levels, suggestive of a common mode of action via inhibition of EGFR signaling. To corroborate these observations, the toxicity profile of AONs was assessed in the presence of erlotinib, a small molecule inhibitor of EGFR kinase activity. In agreement with our hypothesis, the ATP profile of innocuous and toxic AONs was undistinguishable in EGFR-inactivated cells via erlotinib (Figure 4D). Altogether, these data provide strong evidence that inhibition of EGFR signaling may be a central mechanism of AON-induced cytotoxicity in PTEC models. Modulation of EGFR Trafficking and Signaling by Toxic AONs AONs are poly-anionic molecules capable of binding to cell surface proteins and growth factors,21, 22 and it is conceivable that direct AON/EGF or AON/EGFR interactions initiate a negative regulation of EGFR that progressively leads to weakening of EGFR activity and decreased cellular activity. We assessed the direct interactions of five selected AONs with EGF and the extracellular domain of EGFR, separately and in combination, using label-free surface plasmon resonance (SPR). Despite robust interaction between EGF and EGFR, no direct AON/protein interaction could be detected between any of the five tested AONs and EGF or EGFR (Figure S8). Moreover, the data suggest that AONs did not interfere with the binding of EGF to EGFR in a cell-free system. We therefore used a fluorescence-based cellular assay that preserves the native conformation of membrane-bound receptors to visualize the binding of EGF to EGFR and the internalization of the EGF/EGFR complex. Briefly, EGF-starved PTEC-TERT1 were exposed to innocuous and toxic AONs in the presence of a fluorescently labeled EGF (EGF-488) for 10 min on ice to prevent internalization from the plasma membrane. PTEC-TERT1 cells were fixed and EGFR was visualized by immuno-detection. Binding of EGF-488 to the cellular membrane was evident for all conditions including PTEC-TERT1 exposed to toxic AONs (Figure 5A, upper panels). Addition of cetuximab completely abolished the binding of EGF-488 to the cell membrane and thereby confirmed the specific and effective binding of EGF-488 to EGFR for all treatments (Figure 5A, lower panels). Next, to visualize the internalization of EGF/EGFR, PTEC-TERT1 were incubated with EGF-488 at 37°C. Cellular uptake of EGF-488 was evident in both the vehicle and AON-exposed PTEC-TERT1 (Figure 5B, upper panels) and exclusively mediated by EGFR because the addition of cetuximab completely abolished the internalization of EGF-488 in all conditions (Figure 5B, lower panels). In agreement with this image-based assay, quantification by flow cytometry showed similar EGF-488 uptake by PTEC-TERT1 in the presence of innocuous and toxic AONs (Figure S9). We conclude that these AONs do not significantly interfere with EGF binding to EGFR and that simultaneous acute incubation with EGF and AONs does not directly block EGF uptake. Intriguingly, in cells exposed to AONs D, B, C, and E, EGFR was internalized in the presence of cetuximab and was not associated with any detectable EGF-488 signal (Figures 5B and 5C, arrows). In all conditions except vehicle and AON-A, a subpopulation of cells showed a perinuclear distribution of EGFR (Figure 5C, arrows). We developed a method to quantify the presence of EGFR foci located at a fixed distance from the nucleus (perinuclear EGFR) and determined the mean intensity of perinuclear EGFR per cell. In vehicle-treated cells, co-incubation with EGF and cetuximab maintained EGFR at the cell membrane (Figure 5C, arrow), which is translated as a left shift on the quantification graph of perinuclear EGFR (Figure 5D). Incubation with toxic AONs significantly disrupted the cetuximab-dependent distribution of EGFR between the plasma membrane and the perinuclear compartment: the amount of EGFR at the cell membrane was diminished and accumulation of perinuclear EGFR was increased (Figures 5D and S10). The molecular nature of perinuclear EGFR foci caused by toxic AONs, unveiled here by the use of cetuximab, remains to be elucidated in future studies. Nevertheless, these observations suggest that toxic AONs induce ligand-independent internalization of EGFR. Next, the acute effect of AONs on EGFR kinase activity was determined by immunoblot analysis of AKT and ERK1/2 phosphorylation. PTEC-TERT1 were exposed to EGF and AONs and harvested after 10 min of incubation. Downregulation of phosphorylation of AKT by toxic AON-C and E was readily apparent after 10 min of exposure (Figures 5E, left panel, and S11). The effects of toxic AON-B, AON-C, and AON-E on phosphorylation of AKT and ERK1/2 were more pronounced after 24 and 72 hr of AON exposure (Figures 5E, middle and right panels, and S11), likely reflecting a reduced steady-state level of EGFR signaling in toxic AON-exposed cells. Such reduction is not caused by a general toxicity effect, since the nephrotoxicant cyclosporine A (CysA) did not reduce the phosphorylation level of AKT and ERK1/2 relative to the GAPDH protein loading control (Figure S12). The effect of AON-D on EGFR activity could not be detected by measurement of AKT and ERK1/2 phosphorylation level, hypothetically due to compensatory signals or feedback mechanisms, which would also explain the variable profile of AON-D across in vivo studies in rodents (Table 1; Figure S5). Together, these results reveal acute effects of toxic AONs on EGFR cellular distribution and kinase activity and suggest that reduced EGF uptake in toxic AON-exposed PTEC-TERT1 occurs progressively as a consequence of dysfunctional EGFR trafficking and signaling. Impairment of an EGF Transcriptional Signature by Toxic AONs In order to further investigate the effects of AONs on EGF-dependent responses at early time points, we used molecular phenotyping, a recently introduced technology to infer human pathway activities by quantifying expression of pathway-reporter genes with next-generation sequencing.23 PTEC-TERT1 were treated with innocuous and toxic AONs in the presence or absence of EGF for 6 hr, total RNA was isolated and pathway reporter genes were quantified based on sequencing of predefined amplicons.24 To derive a list of genes that are modulated by extracellular EGF in PTEC-TERT1 (EGF signature herein), we compared expression profiles of vehicle-treated cells with and without EGF and identified 66 genes that are consistently positively or negatively modulated by EGF. We performed functional enrichment analysis of EGF signatures and observed that genes induced by EGF have versatile biological functions such as signal transduction, cytokine production, response to oxidative stress and hypoxia, defense response, and fatty acid metabolism (Figure 6A). It is worth mentioning that no gene set directly associated with cell cycle or apoptosis passed the significance threshold. The signature allowed us to interrogate whether AON treatments impaired EGF signaling. Cluster analysis of EGF-induced changes of the signature revealed that treatment with toxic AONs altered the downstream expression output of EGF signaling as early as 6 hr compared with vehicle control. At 30 and 100 μM, the innocuous AON-A and vehicle clustered together while AON-B, AON-C, AON-D, and AON-E displayed substantially different profiles (Figure 6B). Next, we used heatmap visualization of expression changes to compare the effects of AONs on the EGF signature after 6 hr of exposure at 30 μM. The vehicle control highlights positively and negatively regulated genes in the EGF versus no-EGF condition (Figure 6C). The EGF-induced signature (red signals) is preserved in AON A-treated cells consistent with the innocuous profile observed in vitro and in vivo under our experimental conditions. Interestingly, several genes strongly downregulated by the presence of EGF (blue signals) were less modulated in the presence of AON-A, suggesting a general effect of AONs that is not deleterious for normal cellular function. Remarkably, AON-B, AON-C, AON-D, and AON-E almost abolished the EGF signature of both positive and negative EGF-dependent modulation (Figure 6C). Interestingly, all four potentially toxic AONs showed a similar profile in this analysis, including AON-D. Therefore, molecular phenotyping analysis of EGF-induced signature is a sensitive and powerful approach to detect the tubulotoxicity potential of AONs. Overall, molecular phenotyping data revealed that only known toxic AONs inhibit EGF signaling as early as 6 hr after treatment, consistent with molecular and cellular analyses of EGFR signaling. Safety Assessment across Pre-clinical AON Series Using Extracellular EGF To validate the use of EGF as a biomarker in discovery and pre-clinical kidney safety screens, we reviewed pre-clinical studies available to our group and selected an additional 12 LNA-AON compounds targeting MYD88 or BCL11A with reported gross anatomical changes in mouse kidneys or histopathological findings in rat kidneys (Table S1). Two additional innocuous AONs were included as controls. For all 14 AONs",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,63,Acsl1/GR LNA gapmer panel from PMID 27461380,ASO,ACSL1; NR3C1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > In vivo hepatotoxicity of gapmers and ‘non-gapmers’; paragraph 8,2061,Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides.,27461380,PMC4961955,10.1038/srep30377,https://pubmed.ncbi.nlm.nih.gov/27461380/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The Acsl1 gapmer used in this study significantly increases plasma ALT/AST levels within a few days after a single administration.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,64,toxic LNA/MOE gapmer ASO panel from PMID 26553810,ASO,long pre-mRNA transcripts,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > Targeted down-regulation of several long pre-mRNA transcripts by mixtures of MOE ASOs mimics LNA ASOs hepatotoxicity; paragraph 39,2062,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.,26553810,PMC4797265,10.1093/nar/gkv1210,https://pubmed.ncbi.nlm.nih.gov/26553810/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,65,PMO-GF formulation from PMID 26964641,ASO,DMD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety,B,Results > PMO-GF yields long-term efficacy and functional improvement; paragraph 8,4241,Hexose enhances oligonucleotide delivery and exon skipping in dystrophin-deficient mdx mice.,26964641,PMC4793046,10.1038/ncomms10981,https://pubmed.ncbi.nlm.nih.gov/26964641/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Analysis of serum biochemical indices including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, serum creatinine, urea, urinary kidney injury molecule-1 and serum glucose, and histology revealed no evidence of liver or renal toxicity, or abnormal increase in serum glucose levels (Supplementary Fig. 2a–d, n=6) and no inflammatory cell activation (Supplementary Fig. 2e, n=6)",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,66,3-8-3 LNA gapmer hepatotoxicity panel from PMID 24550163,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > Evaluation of hepatotoxicity in mice; paragraph 14,2063,Sequence motifs associated with hepatotoxicity of locked nucleic acid--modified antisense oligonucleotides.,24550163,PMC4005641,10.1093/nar/gku142,https://pubmed.ncbi.nlm.nih.gov/24550163/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Over 80 unique 3-8-3 gapmers targeting the mRNAs for human Apoc3, Crtc2 or GR were tested for tolerability in vivo.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,67,Bepirovirsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Abstract; paragraph 1,1075,"A Phase 1, Randomized, Open-Label, Parallel Group Study to Evaluate the Relative Bioavailability and Safety of Subcutaneous Bepirovirsen when Delivered from a Vial or Prefilled Syringe Fitted with a Safety Syringe Device in Healthy Adult Participants.",41085094,PMC12856967,10.1002/cpdd.1615,https://pubmed.ncbi.nlm.nih.gov/41085094/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"A total of 2 participants reported events within the AESI of ALT increases; 1 participant in the HCP‐administered PFS SSD group, and 1 participant in the self‐administered PFS SSD with training group each reported an AE of ALT increase and aspartate aminotransferase increase",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,68,siRNA candidate from PMID 41076269,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,A,RESULTS > siFibrinogen did not cause adverse effects; paragraph 23,1476,Preclinical safety and bleeding evaluation in swine for a small interfering RNA-lipid nanoparticle that prevents excess fibrinogen synthesis.,41076269,PMC12766900manuscript-id: NIHMS2123465,10.1016/j.jtha.2025.09.012,https://pubmed.ncbi.nlm.nih.gov/41076269/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No infusion-related reactions or toxicity was observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,69,siRNA candidate from PMID 41716677,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Results > Platelet-mediated siRNA delivery exhibits a favorable safety profile; paragraph 32,6238,Spatiotemporal reprogramming of cardiac lipid metabolism by platelet-engineered RNA therapy epigenetically modulate heart repair and regeneration.,41716677,PMC12914854,10.1016/j.bioactmat.2026.02.009,https://pubmed.ncbi.nlm.nih.gov/41716677/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Systemic inflammatory responses were assessed by cytokine profiling, which revealed no significant induction of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, IFN-α, or IFN-γ following siCD36@MSNs@Plt treatment (Fig. S4O)",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,70,siRNA candidate from PMID 40692538,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Drugs-Loaded GalNac-RBC-EVs Were Non-Toxic to Mice; paragraph 42,1242,Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases.,40692538,PMC12277184,10.2147/IJN.S510937,https://pubmed.ncbi.nlm.nih.gov/40692538/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No significant toxicity was observed in vital organs (ALT/AST levels, P>0.05; histopathology scores, P>0.05).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,71,Plozasiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Safety; paragraph 28,1532,"Safety, pharmacokinetics and pharmacodynamics of Plozasiran in Chinese healthy volunteers.",41094680,PMC12523034,10.1186/s12933-025-02929-9,https://pubmed.ncbi.nlm.nih.gov/41094680/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There were no reported TEAEs that led to withdrawal from the trial, no serious TEAEs or treatment-induced SAEs occurred, and no deaths were reported during the study period.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,72,siRNA candidate from PMID 40825982,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > LNPs biodistribution to the inflamed colon; paragraph 17,1815,Targeting intestinal inflammation using locked nucleic acids delivered via lipid nanoparticles.,40825982,PMC12361575,10.1038/s41467-025-63037-6,https://pubmed.ncbi.nlm.nih.gov/40825982/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The enzymes ALP, ALT, and AST, remained at the same level in all treated groups when compared to the healthy group (Fig. 6g–i), indicating the absence of inflammation and liver toxicity",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,74,siRNA candidate from PMID 40314193,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Introduction; paragraph 7,3700,Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection.,40314193,PMC12051533,10.1080/13880209.2025.2498169,https://pubmed.ncbi.nlm.nih.gov/40314193/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"These findings demonstrate that the toxicity of the three new LNPs was consistent across all three cell types, with no significant change in cell viability within the concentration range tested.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,75,siRNA candidate from PMID 41214041,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results > Evaluation of the cytotoxicity and siRNA transfection efficiency of LaN; paragraph 27,7859,LINC02178 drives lung adenocarcinoma progression and serves as a therapeutic target for nanodelivery-based intervention.,41214041,PMC12603185,10.1038/s41598-025-22922-2,https://pubmed.ncbi.nlm.nih.gov/41214041/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Compared with those in the control group, no significant differences in tissue integrity or cellular morphology were observed in the experimental group (Fig. 7).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,76,siRNA candidate from PMID 40503175,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Therapeutic potential of GalNAc-siCIDEB in MASH; paragraph 16,9324,Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models.,40503175,PMC12156227,10.1016/j.omtn.2025.102567,https://pubmed.ncbi.nlm.nih.gov/40503175/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Histological analysis revealed no treatment-related liver abnormalities, including fibrosis, necrosis, or hepatocellular degeneration (Figure 3G).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,77,siRNA candidate from PMID 39896757,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Discussion; paragraph 45,12278,Isoprenaline-Modified Polyethyleneimine as an Efficient Gene Delivery System for Targeted Asthma Therapy and Airway Remodeling Inhibition.,39896757,PMC11782793,10.34133/bmr.0136,https://pubmed.ncbi.nlm.nih.gov/39896757/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 39896757; pmc_full_text evidence was direct but less than full primary-detail confidence for renal/renal safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,78,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results; paragraph 18,2609,Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.,38371290,PMC10866732,10.1016/j.jacasi.2023.09.006,https://pubmed.ncbi.nlm.nih.gov/38371290/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,TEAEs associated with hepatic safety were balanced between the treatment groups (inclisiran group: 12.4%; placebo group: 10.9%).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,79,ASO candidate from PMID 37365583,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Safety of LNA-i-miR-221; paragraph 28,1167,"Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.",37365583,PMC10294514,10.1186/s13045-023-01468-8,https://pubmed.ncbi.nlm.nih.gov/37365583/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"LNA-i-miR-221 was well tolerated at all dose levels, with no grade 3–4 dose-limiting toxicity (DLT) observed in any cohort.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,81,ASO candidate from PMID 28853853,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,article body; paragraph 5,2231,BNA(NC) Gapmers Revert Splicing and Reduce RNA Foci with Low Toxicity in Myotonic Dystrophy Cells.,28853853,PMC5694563manuscript-id: NIHMS917707,10.1021/acschembio.7b00416,https://pubmed.ncbi.nlm.nih.gov/28853853/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Cytotoxicity was only elevated in cells treated with the positive control digitonin, indicating the ASOs tested do not display cytotoxic effects at 30 nM (Figure S2B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,83,Imetelstat,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,C,Abstract; paragraph 1,8005,US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia.,41135032,PMC12614338manuscript-id: NIHMS2109501,10.1200/JCO-25-01369,https://pubmed.ncbi.nlm.nih.gov/41135032/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Common treatment-emergent adverse reactions (TEAR) in the imetelstat arm, including laboratory abnormalities, were decreased platelets, white blood cells, and neutrophils, increased AST, alkaline phosphatase, and ALT",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,84,Inotersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Safety and tolerability > Thrombocytopenia and glomerulonephritis; paragraph 30,1658,Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial.,32343462,PMC7496583,10.1111/ene.14285,https://pubmed.ncbi.nlm.nih.gov/32343462/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,85,ASO candidate from PMID 41978261,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Results > Kinetics of cytokines released in response to PS ASOs vary according to sequence and chemistry; paragraph 30,1043,Phosphorothioate antisense oligonucleotide induced innate immune activation is attenuated by tryptophan oxidation products.,41978261,PMC13076217,10.1093/nar/gkag311,https://pubmed.ncbi.nlm.nih.gov/41978261/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Considering all the cytokines evaluated, these data show that PS-ASOs segregate into multiple classes based on the extent of innate immune activation and the kinetics of cytokine induction",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,86,SRN001,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Safety Assessment; paragraph 23,1149,"Safety and Pharmacokinetics of SRN001, a Novel siRNA Drug Targeting Amphiregulin via the SAMiRNA Platform.",42052104,PMC13112037,10.2147/DDDT.S589997,https://pubmed.ncbi.nlm.nih.gov/42052104/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Among 25 participants, SRN001 was generally well tolerated.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,87,Alox15-targeting siRNA from PMID 41847300,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results > Assessing in vivo LNP safety: biochemical indicators and vital organ health; paragraph 29,1202,Dual knockdown of Alox15 and TGF-β1 by lipid nanoparticle-delivered siRNA in bleomycin-induced pulmonary fibrosis.,41847300,PMC12990253,10.1016/j.bbrep.2026.102534,https://pubmed.ncbi.nlm.nih.gov/41847300/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No in vivo toxicity observed in mice treated with LNPs encapsulating siRNAs, as analyzed with biochemical indicators in vital organs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,88,ASO candidate from PMID 39850319,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > SGLT2-SNA2-ASO suppressed renal SGLT2 expression without severe liver and renal tubular damage; paragraph 12,1041,In vivo efficacy and safety of systemically administered serinol nucleic acid-modified antisense oligonucleotides in mouse kidney.,39850319,PMC11754010,10.1016/j.omtn.2024.102387,https://pubmed.ncbi.nlm.nih.gov/39850319/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,These data indicated that SNA2-ASO was safer than MOE-ASO in terms of adverse hepatic and renal events.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,89,ASO candidate from PMID 40243849,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,2. Results > 2.4. MSTN-ASO Treatment Does Not Affect Kidney Functions; paragraph 15,1262,Inhibiting Myostatin Expression by the Antisense Oligonucleotides Improves Muscle Wasting in a Chronic Kidney Disease Mouse Model.,40243849,PMC11988723,10.3390/ijms26073098,https://pubmed.ncbi.nlm.nih.gov/40243849/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40243849; pmc_full_text evidence was direct but less than full primary-detail confidence for renal/renal safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,90,TLR9-targeted; STAT3; PD1-targeting ASO from PMID 40214214,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Results > Reduced IFN-I-Related Neurotoxicities after Intracranial Administration of CpG-STAT3dsASO; paragraph 29,1843,Multimodal glioma immunotherapy combining TLR9-targeted STAT3 antisense oligodeoxynucleotides with PD1 immune checkpoint blockade.,40214214,PMC12526143,10.1093/neuonc/noaf099,https://pubmed.ncbi.nlm.nih.gov/40214214/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"CpG-ssSTAT3ASOLNA treatment increased average ATSS score across all tested doses (0.1-1 mg/kg) with marked signs of toxicity, including decreased consciousness and impaired movement at the highest dose",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,91,Imetelstat,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Abstract; paragraph 1,2111,"No Effect of Immunogenicity on Pharmacokinetics, Efficacy, and Safety of the Oligonucleotide Telomerase Inhibitor Imetelstat in Lower-Risk Myelodysplastic Syndromes.",41390988,PMC12702135,10.1111/cts.70431,https://pubmed.ncbi.nlm.nih.gov/41390988/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The rates of drug‐related grade ≥ 3, serious, or fatal TEAEs were similar or lower in ADA‐positive versus ADA‐negative patients.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,92,siRNA candidate from PMID 41625362,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Discussion; paragraph 29,3396,Tumor-homing exosomes enable targeted delivery of siRNA and isoimperatorin for overcoming BTK inhibitor resistance in DLBCL.,41625362,PMC12859616,10.1016/j.mtbio.2025.102267,https://pubmed.ncbi.nlm.nih.gov/41625362/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 41625362; pmc_full_text evidence was direct but less than full primary-detail confidence for immunotoxicity/immune activation.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,93,siRNA candidate from PMID 41360814,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > Biodistribution of the nanodevice; paragraph 11,3423,Inflammation-specific DNA origami nanodevice for delivery of siRNAs to treat ulcerative colitis.,41360814,PMC12804779,10.1038/s41467-025-67183-9,https://pubmed.ncbi.nlm.nih.gov/41360814/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The nanodevice exhibited good in vivo biosafety, with no observed toxicity to the liver or kidneys, and no abnormalities in serum biochemical indices (Supplementary Fig. 22).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,94,CD11b-modified-targeting siRNA from PMID 40977834,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > In vivo biosafety assessment; paragraph 50,3501,CD11b-modified ROS/pH-responsive nanoparticles co-deliver Dioscin and siRNA to improve cardiac repair after myocardial infarction by reducing neutrophil recruitment.,40977834,PMC12446780,10.1016/j.mtbio.2025.102226,https://pubmed.ncbi.nlm.nih.gov/40977834/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40977834; pmc_full_text evidence was direct but less than full primary-detail confidence for renal/renal safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,95,siRNA candidate from PMID 40380202,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Methods > Biosafety of nanodrug; paragraph 27,3685,A novel pH-sensitive nanoparticles encapsulating anti-PD-1 antibody and MDK-siRNA overcome immune checkpoint blockade resistance in HCC via reshaping immunosuppressive TME.,40380202,PMC12082952,10.1186/s13046-025-03396-6,https://pubmed.ncbi.nlm.nih.gov/40380202/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40380202; pmc_full_text evidence was direct but less than full primary-detail confidence for immunotoxicity/immune activation.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,96,Angptl4-targeting ASO from PMID 39259836,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,A,Results > Short-term liver-targeted Angptl3 and Angptl4 silencing does not induce hepatic inflammation; paragraph 27,1565,Liver-targeted Angptl4 silencing by antisense oligonucleotide treatment attenuates hyperlipidaemia and atherosclerosis development in APOE*3-Leiden.CETP mice.,39259836,PMC11687395,10.1093/cvr/cvae195,https://pubmed.ncbi.nlm.nih.gov/39259836/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,a 4-week toxicology study in cynomolgus monkeys showed that anti-ANGPTL4 ASO treatment (weekly subcutaneous injections of up to 30 mg/kg) was well tolerated and did not induce any adverse effects,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,97,siRNA candidate from PMID 39606561,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > Biocompatibility of MPDA Nanodrugs; paragraph 43,12439,A Multifunctional Nanodrug Co-Delivering VEGF-siRNA and Dexamethasone for Synergistic Therapy in Ocular Neovascular Diseases.,39606561,PMC11598607,10.2147/IJN.S492363,https://pubmed.ncbi.nlm.nih.gov/39606561/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"H&E staining also revealed no noticeable pathological abnormalities in the eyes (including eyeball, cornea, and retina) (Figures 6F and 7E) and major organs (including heart, liver, spleen, lung, and kidney)",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,99,siRNA candidate from PMID 38089931,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,B,Results > D-siRNA has a better safety profile; paragraph 15,1117,"Dendritic amphiphilic siRNA: Selective albumin binding, in vivo efficacy, and low toxicity.",38089931,PMC10711485,10.1016/j.omtn.2023.102080,https://pubmed.ncbi.nlm.nih.gov/38089931/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The data showed no detectable alteration of parameters in D-siRNA-injected mice compared with PBS-injected mice,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,100,ASO candidate from PMID 36631935,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,RESULTS > Correlations identified using adverse event network analysis; FIGURE 1 caption,1148,Correlations between preclinical BJAB assay ranking of antisense drugs and clinical trial adverse events.,36631935,PMC10087069,10.1111/cts.13476,https://pubmed.ncbi.nlm.nih.gov/36631935/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse events associated with FLRs were more strongly correlated with the inflammation signals predicted by the BJAB assay than adverse events associated with injection site reactions.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,101,ASO candidate from PMID 37346977,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,B,Results > LNPs increase TA2 potency in vitro by decreasing lysosomal trafficking or increasing ASO uptake; paragraph 11,1479,Lipid nanoparticle delivery limits antisense oligonucleotide activity and cellular distribution in the brain after intracerebroventricular injection.,37346977,PMC10280097,10.1016/j.omtn.2023.05.005,https://pubmed.ncbi.nlm.nih.gov/37346977/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,ASO delivery via both gymnosis and LNPs triggered an ASO-mediated microgliosis response that was evident by increased Iba1 signal and transcriptional activation of inflammatory pathways in the brain.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,102,siRNA candidate from PMID 38168301,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Results > Gender differences; paragraph 25,3970,Evaluation of mAb 2C5-modified dendrimer-based micelles for the co-delivery of siRNA and chemotherapeutic drug in xenograft mice model.,38168301,PMC10760232,10.21203/rs.3.rs-3713164/v1,https://pubmed.ncbi.nlm.nih.gov/38168301/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Despite a higher DOX concentration and residence time we did not observe any systemic toxicities in the nanoparticle groups.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,104,Bepirovirsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 52,1460,"Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus-Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses.",35971951,PMC9804925,10.1002/cpdd.1154,https://pubmed.ncbi.nlm.nih.gov/35971951/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"across the single and multiple dose cohorts, 197 treatment‐emergent adverse events were reported, with 99% and 65% classified as mild in severity and local injection site reactions, respectively.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,105,ASO candidate from PMID 33567808,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,B,Results > 2’MOE ASO (104838 and 501861) and CpG ASO increase platelet P-selectin expression in platelet-rich plasma and whole blood; Figure 1. caption,2730,"Sequence-specific 2'-O-methoxyethyl antisense oligonucleotides activate human platelets through glycoprotein VI, triggering formation of platelet-leukocyte aggregates.",33567808,PMC8804562,10.3324/haematol.2020.260059,https://pubmed.ncbi.nlm.nih.gov/33567808/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,104838 and 501861 triggered moderate platelet activation and sykdependent formation of platelet-leukocyte aggregates.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,106,siRNA candidate from PMID 35992044,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Delivery of antiviral antigens simultaneously in vitro; paragraph 22,12550,A model system for antiviral siRNA therapeutics using exosome-based delivery.,35992044,PMC9384066,10.1016/j.omtn.2022.08.011,https://pubmed.ncbi.nlm.nih.gov/35992044/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"When treated with either exosomes alone, EPM, or EPM loaded with nucleic acids as used in this study, HEK293T cells had similar survival as compared to untreated cells, indicating the lack of detectable cytotoxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,107,siRNA candidate from PMID 30544191,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,RESULTS > The chemical nature of the lipid conjugate defines the liver/kidney distribution profile; paragraph 29,12615,Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo.,30544191,PMC6379722,10.1093/nar/gky1239,https://pubmed.ncbi.nlm.nih.gov/30544191/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Our study found that some lipid conjugates, particularly DCA and PC-DCA, support higher siRNA accumulation than cholesterol in extra-hepatic tissues, including muscle, heart, fat and lung, without causing overt toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,108,ASO candidate from PMID 29107969,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Results > Immunostimulatory effect of ONs; paragraph 44,2321,Assessing single-stranded oligonucleotide drug-induced effects in vitro reveals key risk factors for thrombocytopenia.,29107969,PMC5673186,10.1371/journal.pone.0187574,https://pubmed.ncbi.nlm.nih.gov/29107969/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,phosphorothioate (PS)-ONs can bind to platelet proteins such as platelet collagen receptor glycoprotein VI (GPVI) and activate human platelets in vitro to various extents.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,109,siRNA candidate from PMID 40654369,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results > HPssPT delivers siRNA into HCC cells with potent transfection efficiency and favorable safety performance; paragraph 47,9006,Silencing PTPN2 with nanoparticle-delivered small interfering RNA remodels tumor microenvironment to sensitize immunotherapy in hepatocellular carcinoma.,40654369,PMC12254698,10.1016/j.apsb.2025.03.015,https://pubmed.ncbi.nlm.nih.gov/40654369/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,HA/PEIss@siNC (HPssNC) at various concentrations revealed no significant changes in cell viability (Fig. 2F).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,110,Nedosiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > Safety; paragraph 24,10207,"Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).",39875734,PMC12031765,10.1007/s00467-025-06675-8,https://pubmed.ncbi.nlm.nih.gov/39875734/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Median percent change from baseline in eGFR was 2.5%, indicating preservation of renal function.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,111,Nedosiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > Participants; paragraph 20,2597,Nedosiran Safety and Efficacy in PH1: Interim Analysis of PHYOX3.,38707801,PMC11068990,10.1016/j.ekir.2024.02.1439,https://pubmed.ncbi.nlm.nih.gov/38707801/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,mean estimated glomerular filtration rate (egfr) remained stable (62–84.2 ml/min per 1.73 m2) to month 30.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,112,DNA/RNA heteroduplex oligonucleotide candidate from PMID 39252874,DNA/RNA heteroduplex oligonucleotide,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,B,Results > The effect of HDO formation on class-related toxicities; paragraph 7,10778,DNA/RNA heteroduplex technology with cationic oligopeptide reduces class-related adverse effects of nucleic acid drugs.,39252874,PMC11382116,10.1016/j.omtn.2024.102289,https://pubmed.ncbi.nlm.nih.gov/39252874/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,HDOs significantly decreased C3a levels compared to ASOs in both base lengths in the ex vivo assay (Figures 1E and 1F).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,113,Viltolarsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,RESULTS > Safety; paragraph 21,1602,"Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study.",37005891,PMC10200237,10.3233/JND-221656,https://pubmed.ncbi.nlm.nih.gov/37005891/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Laboratory data on renal function (including cystatin C) were followed for the whole length of the study, with no clinically significant findings being reported.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,114,Viltolarsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,RESULTS > Safety; paragraph 21,1621,Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.,35634851,PMC9398057,10.3233/JND-220811,https://pubmed.ncbi.nlm.nih.gov/35634851/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Safety was similar to that observed in the previous 24-week trial, which was predominantly mild.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,115,ASO candidate from PMID 32530964,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Conclusion; paragraph 41,1431,Refining LNA safety profile by controlling phosphorothioate stereochemistry.,32530964,PMC7292364,10.1371/journal.pone.0232603,https://pubmed.ncbi.nlm.nih.gov/32530964/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,when tested in primary mouse hepatocytes and human proximal tubular epithelial cells treatment with c1 resulted in “severe toxicity” in both cell systems.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,116,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,RESULTS > Safety Evaluation; paragraph 46,2299,"Efficacy, Safety, and Tolerability of Inclisiran in Patients With Homozygous Familial Hypercholesterolemia: Results From the ORION-5 Randomized Clinical Trial.",37850379,PMC10815002,10.1161/CIRCULATIONAHA.122.063460,https://pubmed.ncbi.nlm.nih.gov/37850379/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,117,siRNA candidate from PMID 41949334,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Treatment of Hepatic Spheroids With Chemically Modified GalNAc‐Conjugated siRNA; FIGURE 2 caption,1059,A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.,41949334,PMC13059674,10.1111/cts.70536,https://pubmed.ncbi.nlm.nih.gov/41949334/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No signs of hepatotoxicity were observed under the conditions used.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,118,ASO candidate from PMID 41754970,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,3. Results and Discussions > 3.3. In Vitro Delivery of Splice-Switch ASO; paragraph 26,1065,Unconventional Lysine-Type Lipid Assemblies Enable Efficient Antisense Oligonucleotide Delivery with Distinct Structural Features.,41754970,PMC12944301,10.3390/pharmaceutics18020228,https://pubmed.ncbi.nlm.nih.gov/41754970/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"in spleen cells, no noticeable cytotoxicity was observed at concentrations up to 100 µm (figure 2).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,119,Vutrisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,C,Discussion; paragraph 43,1173,Assessing the real-world safety of vutrisiran for transthyretin-mediated amyloidosis with polyneuropathy: Based on WHO-VigiAccess and FAERS databases.,41984862,PMC13082648,10.1371/journal.pone.0347417,https://pubmed.ncbi.nlm.nih.gov/41984862/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 41984862; weak/generic or abstract-limited support for neurological/neurotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,120,ASO candidate from PMID 41399312,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results and Discussion; paragraph 25,1215,Delivery of Antisense Oligonucleotides Using the Nano-Cell Vesicle Technology System (nCVTs) for Targeted Cancer Therapy.,41399312,PMC12877987,10.1002/smll.202509094,https://pubmed.ncbi.nlm.nih.gov/41399312/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Remarkably, both ALT and creatinine concentrations remained comparable to control levels, indicating that our treatment did not induce any significant liver or kidney toxicity (Figure S8B,C, Supporting Information).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,121,siRNA candidate from PMID 41755009,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,3. Results and Discussion > 3.12. Assessment of Biochemical Parameters; paragraph 53,1744,Calcium/Aluminum-Cored Asymmetric Bilayer Nanoparticles for Codelivery of Ziyuglycoside II and PD-L1 siRNA Exert Anti-Breast Tumor Effects.,41755009,PMC12944025,10.3390/pharmaceutics18020268,https://pubmed.ncbi.nlm.nih.gov/41755009/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 41755009; pmc_full_text evidence was direct but less than full primary-detail confidence for renal/renal safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,123,siRNA candidate from PMID 41477663,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Results and discussion > Biosafety of MnO2 nanozymes; paragraph 22,3330,Chiral metal nanozyme-enabled SOD2 activation and siRNA delivery cooperatively mitigating chronic heart failure.,41477663,PMC12752751,10.1016/j.bioactmat.2025.11.049,https://pubmed.ncbi.nlm.nih.gov/41477663/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Collectively, these results indicate that the chiral MnO2 nanozymes did not induce detectable adaptive immune activation and exhibited excellent biosafety in vivo.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,124,siRNA candidate from PMID 41896932,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Result and discussion > In vivo safety assessment; paragraph 61,5624,Overcoming lysosomal barrier via V-ATPase: an exosome-based co-delivery platform for combined chemo/RNAi therapy against breast cancer.,41896932,PMC13151111,10.1186/s12951-026-04311-7,https://pubmed.ncbi.nlm.nih.gov/41896932/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,in vivo studies validated that the nano-delivery system exhibits potent antitumor efficacy in a 4T1 murine breast cancer model while maintaining a favorable biosafety profile.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,125,Nusinersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Abstract; paragraph 6,1015,Safety and Efficacy of Nusinersen Focusing on Renal and Hematological Parameters in Spinal Muscular Atrophy.,39829133,PMC11743982,10.1002/brb3.70221,https://pubmed.ncbi.nlm.nih.gov/39829133/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No significant adverse effects on platelet counts or renal functions were observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,126,Pelacarsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Introduction; paragraph 4,1030,"Pharmacokinetics and Safety of Pelacarsen, a GalNAc(3)-Conjugated Antisense Oligonucleotide Targeting Apo(a), in Participants With Mild Hepatic Impairment.",41021771,PMC12478598,10.1111/cts.70344,https://pubmed.ncbi.nlm.nih.gov/41021771/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No safety concerns were identified in participants with mild HI or in matched controls.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,127,RO7239958,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,C,INTRODUCTION; paragraph 4,1040,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.",41186228,PMC12691668,10.1128/aac.00679-25,https://pubmed.ncbi.nlm.nih.gov/41186228/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"RO7239958 was generally well tolerated in healthy volunteers; transaminase elevations occurred at the highest doses, including one reversible Grade 3 elevation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,128,ASO candidate from PMID 40654713,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,C,Abstract; paragraph 1,1160,"Anti-Sense Oligonucleotide as a Therapeutic for Synucleinopathies: Pharmacokinetic, Safety and Efficacy Evaluation.",40654713,PMC12247940,10.1101/2025.05.01.651722,https://pubmed.ncbi.nlm.nih.gov/40654713/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40654713; weak/generic or abstract-limited support for neurological/neurotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,129,ASO candidate from PMID 41169576,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results and Discussion > Reduction of Hepatotoxicity by scpBNA Series; paragraph 23,1408,"Cycloalkane Incorporation Into the 2',4'-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides.",41169576,PMC12569656,10.1021/jacsau.5c01005,https://pubmed.ncbi.nlm.nih.gov/41169576/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"ON30 effectively reduced liver Nr3c1 expression but caused significant hepatotoxicity, as evidenced by elevated ALT and AST levels and reduced body weight",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,130,ASO/siRNA mixed context candidate from PMID 41268339,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Results and discussion > Discussion; paragraph 49,1791,A naturally derived lipopeptide lipid nanoparticle platform enabling multiple nucleic acids delivery.,41268339,PMC12628137,10.1016/j.bioactmat.2025.09.007,https://pubmed.ncbi.nlm.nih.gov/41268339/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"RmHnC-DOPE LNPs did not induce any abnormal elevations in biochemical parameters, indicating well-preserved hepatic and renal functions.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,131,siRNA candidate from PMID 41439881,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,3. Results and Discussion > 3.3. Cytotoxicity Studies > 3.3.1. MTT Cytotoxicity Assay; paragraph 40,2096,"Biocompatible Copolymerized Gold Nanoclusters: Anti-TNF-α siRNA Binding, Cellular Uptake, Cytotoxicity, Oxidative Stress and Cell Cycle Effects In Vitro.",41439881,PMC12730731,10.3390/biomimetics10120812,https://pubmed.ncbi.nlm.nih.gov/41439881/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"cell viabilities remained above this threshold, indicating that all nanocomplexes were non-toxic in all cells.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,132,siRNA candidate from PMID 40911569,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,3 Results and discussion > 3.7. Sub-acute skin toxicity of PF127 gel > 3.7.5. Assessment of renal function and potential toxicity.; paragraph 102,2098,"Upscaling, toxicity and efficacy of multifaceted dressing embedded with dsirna-loaded gold nanoparticles for enhancing diabetic wound treatment.",40911569,PMC12412931,10.1371/journal.pone.0327375,https://pubmed.ncbi.nlm.nih.gov/40911569/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,indicating no renal injury or abnormalities in renal function.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,134,ASO candidate from PMID 40604820,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Result and discussion > In-vitro cytotoxicity evaluation of surface-modified USMP; paragraph 45,2483,Ultrasmall nanoparticles for co-delivery of antisense oligonucleotides targeting miR-21 and miR-210 to treat glioblastoma.,40604820,PMC12225093,10.1186/s12951-025-03529-1,https://pubmed.ncbi.nlm.nih.gov/40604820/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We have successfully demonstrated that by optimizing the PEI ratio with close to neutral surface charge, we were able to reduce PEI-induced cytotoxicity without compromising the transfection efficiency.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,135,siRNA candidate from PMID 40006524,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,"3. Results and Discussion > 3.7. Toxicity Evaluation of Heart, Kidney, Liver, and Spleen; paragraph 55",2526,Engineering Lipid Nanoparticles to Enhance Intracellular Delivery of Transforming Growth Factor-Beta siRNA (siTGF-β1) via Inhalation for Improving Pulmonary Fibrosis Post-Bleomycin Challenge.,40006524,PMC11859093,10.3390/pharmaceutics17020157,https://pubmed.ncbi.nlm.nih.gov/40006524/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"no obvious toxicity-related lesions were observed in the heart, liver, spleen, lung, and kidneys of mice treated with",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,136,Fitusiran,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Results > Safety; paragraph 20,2538,"Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B.",39642315,PMC11914172,10.1182/bloodadvances.2024013900,https://pubmed.ncbi.nlm.nih.gov/39642315/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"After implementation of the AT-based dose regimen, there were no thrombotic events, and a reduction in the incidence of elevated transaminases and biliary events was reported.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,137,Ce6-targeting siRNA from PMID 41299672,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results and discussion > Preparation and characterization of si-Ce6@tLyP-1-NPs; paragraph 13,3428,Peptide-modified phase-transition nanoparticles co-deliver FTO siRNA and Ce6 for sonodynamic metabolism-immunotherapy of melanoma.,41299672,PMC12837076,10.1186/s12951-025-03872-3,https://pubmed.ncbi.nlm.nih.gov/41299672/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 41299672; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,138,siRNA candidate from PMID 41007671,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,4. Discussion; paragraph 29,3493,Crossing Barriers: PEGylated Gold Nanoparticles as Promising Delivery Vehicles for siRNA Delivery in Alzheimer's Disease.,41007671,PMC12467891,10.3390/biomedicines13092108,https://pubmed.ncbi.nlm.nih.gov/41007671/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Both tested nanoparticles proved to be less genotoxic when they were complexed with siRNA, showing a DNA disruption at levels below 10%",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,140,siRNA candidate from PMID 40433119,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results and Discussion > Biochemical Parameter Determination; paragraph 50,3666,Lipid-Coated Ag@MnO(2) Core-Shell Nanoparticles for Co-Delivery of Survivin siRNA in Breast Tumor Therapy.,40433119,PMC12106909,10.2147/IJN.S510514,https://pubmed.ncbi.nlm.nih.gov/40433119/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"we observed no significant changes in the levels of biochemical indicators (including AST, ALT, BUN, and CRE-L) in the treatment groups relative to the model group, confirming the absence of damage to the normal liver and kidney functions",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,141,siRNA candidate from PMID 39990947,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results and Discussion > Safety Profile of DDAB-cLNPs on Liver Cancer Cells; paragraph 28,3749,Development of Small Interfering RNA Loaded Cationic Lipid Nanoparticles for the Treatment of Liver Cancer with Elevated α-Fetoprotein Expression.,39990947,PMC11843345,10.1021/acsbiomedchemau.4c00061,https://pubmed.ncbi.nlm.nih.gov/39990947/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,no significant toxicity of siSCR-loaded DDAB-cLNPs (siSCR@DDAB-cLNPs) was observed across all concentrations,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,142,Imetelstat,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Introduction; paragraph 4,3751,"Low Proarrhythmic Risk of Imetelstat, a Novel Oligonucleotide Telomerase Inhibitor: A Translational Analysis.",39980062,PMC11842220,10.1111/cts.70169,https://pubmed.ncbi.nlm.nih.gov/39980062/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Clinical evaluations showed no significant effects on QTcF or other electrocardiogram parameters at 7.1 mg/kg.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,143,siRNA candidate from PMID 39934917,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Discussion; paragraph 15,3759,Development and evaluation of siRNA-mediated gene silencing strategies for ADO2 therapy utilizing iPSCs model and DMPC-SPIONs delivery system.,39934917,PMC11816505,10.1186/s13287-025-04151-6,https://pubmed.ncbi.nlm.nih.gov/39934917/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The CCK-8 assay results indicate that the cell viability of each experimental group exceeded 97%,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,144,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Abstract > Methods and results; paragraph 2,8812,Systemic evaluation of inclisiran on the risk of new-onset diabetes and hyperglycemia compared to evolocumab and atorvastatin.,40735483,PMC12303805,10.3389/fphar.2025.1554631,https://pubmed.ncbi.nlm.nih.gov/40735483/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Atorvastatin had a higher ROR for type 2 diabetes (195.03) than inclisiran (0.95) and evolocumab, but it was not statistically significant.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,145,siRNA candidate from PMID 40444266,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results and Discussion > In vivo biosafety evaluation; paragraph 42,9437,Reactive Oxygen Species-Responsive Ferrocene Nanoparticles Delivering Small Interfering RNA Targeting NOP2/Sun RNA Methyltransferase Family Member 2 for Gastric Cancer Therapy.,40444266,PMC12120247,10.34133/bmr.0209,https://pubmed.ncbi.nlm.nih.gov/40444266/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"no significant differences in the levels of ALT, AST, UREA, CRE, RBC, WBC, HGB, and PLT among the treatment groups.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,147,Nusinersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Safety of nusinersen sodium injection for the treatment of SMA; paragraph 41,12141,Real-world analysis of the efficacy and safety of nusinersen in pediatric patients with spinal muscular atrophy.,40011938,PMC11866593,10.1186/s13023-025-03603-9,https://pubmed.ncbi.nlm.nih.gov/40011938/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Regarding safety, the incidence of adverse events was 40.48%, with fever being the most common adverse reaction, occurring in 36.36% of cases.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,148,siRNA candidate from PMID 41304812,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,C,3. Results and Discussion; paragraph 21,12342,Heterofunctional Cationic Polyester Dendrimers as Potent Nonviral Vectors for siRNA Delivery.,41304812,PMC12655120,10.3390/pharmaceutics17111476,https://pubmed.ncbi.nlm.nih.gov/41304812/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Lactate dehydrogenase (LDH) release assays in T98G glioblastoma cells demonstrated excellent biocompatibility of both dendritic families.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,149,PMO candidate from PMID 39119918,PMO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,C,Discussion; paragraph 46,1135,"Efficacy, biodistribution and safety comparison of chemically modified antisense oligonucleotides in the retina.",39119918,PMC11417397,10.1093/nar/gkae686,https://pubmed.ncbi.nlm.nih.gov/39119918/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,octa-guanidine-dendrimer-conjugated in vivo PMO-oligonucleotides (ivPMO) caused toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,150,Olezarsen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,A,Results > Primary endpoint: safety results; paragraph 19,1286,Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans.,39363329,PMC11448427,10.1186/s12944-024-02297-5,https://pubmed.ncbi.nlm.nih.gov/39363329/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,151,ASO/siRNA mixed context candidate from PMID 38271438,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Clinical trial results > Safety; paragraph 32,1290,A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.,38271438,PMC10810432,10.1371/journal.pone.0294847,https://pubmed.ncbi.nlm.nih.gov/38271438/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There were no serious adverse events (SAEs) or suspected or unexpected serious adverse reactions (SUSARs).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,152,siRNA candidate from PMID 39539730,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Results and discussion > Design of gelasomes; paragraph 27,2104,Gelatin and lipidoid integrate to create gelasomes to enhance siRNA delivery with low toxicity.,39539730,PMC11558258,10.1016/j.bioactmat.2024.06.008,https://pubmed.ncbi.nlm.nih.gov/39539730/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"toxicity studies in mice indicate that repeated administration of Gelasomes (up to 48 mg/kg BW) is well-tolerated with no notable changes in body weight, hematology, or serum chemistry.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,153,Fesomersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematologic,platelet/bleeding safety,C,Abstract; paragraph 1,2297,"Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers.",38563414,PMC10985948,10.1111/cts.13784,https://pubmed.ncbi.nlm.nih.gov/38563414/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 38563414; weak/generic or abstract-limited support for hematologic/platelet/bleeding safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,154,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results; paragraph 46,2621,"Efficacy, Safety, and Pharmacokinetics of Inclisiran in Japanese Patients: Results from ORION-15.",38220186,PMC11150722,10.5551/jat.64454,https://pubmed.ncbi.nlm.nih.gov/38220186/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The incidence of TEAEs associated with the liver was higher in the inclisiran sodium 300 mg group, but all were mild in severity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,155,siRNA candidate from PMID 38126895,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Introduction; paragraph 2,3961,Pulmonary siRNA Delivery with Sophisticated Amphiphilic Poly(Spermine Acrylamides) for the Treatment of Lung Fibrosis.,38126895,PMC7616748manuscript-id: EMS199502,10.1002/smll.202308775,https://pubmed.ncbi.nlm.nih.gov/38126895/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"For most of the tested cytokines, P(SpAA-co-DAA)3 treated mice showed similar or lower levels of inflammation than untreated mice (IL-23, IL-27, IFN-y, IL-12p70, IL-10, IFN-b).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,156,siRNA candidate from PMID 39274180,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,4. Discussion; paragraph 46,12106,Chitosan siRNA Nanoparticles Produce Significant Non-Toxic Functional Gene Silencing in Kidney Cortices.,39274180,PMC11398103,10.3390/polym16172547,https://pubmed.ncbi.nlm.nih.gov/39274180/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Pro-inflammatory type-I cytokines (IL-1β, TNF-α, INFγ, IL-6 and KC) measured in serum 4 h post-injection were markedly increased by bacterial LPS and InvLNPs (Figure 4). No significant induction was observed with uncoated and HA-coated NPs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,157,siRNA candidate from PMID 39684325,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,2. Results and Discussion > 2.3. Biological Activity of Dendrimer/siRNA Complexes > 2.3.3. Cytotoxic Effect of Dendrimers and Their Complexes with siRNAs on HeLa Cells; paragraph 30,12433,Non-Viral Systems Based on PAMAM-Calix-Dendrimers for Regulatory siRNA Delivery into Cancer Cells.,39684325,PMC11641217,10.3390/ijms252312614,https://pubmed.ncbi.nlm.nih.gov/39684325/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,PAMAM-calix-dendrimers are low-toxic at the concentration required for efficient RNA binding.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,158,ASO candidate from PMID 39329032,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Introduction; paragraph 5,12464,Ion Doped Hollow Silica Nanoparticles as Promising Oligonucleotide Delivery Systems to Mesenchymal Stem Cells.,39329032,PMC11424689,10.2147/IJN.S461167,https://pubmed.ncbi.nlm.nih.gov/39329032/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,HSN were biocompatible in hMSCs up to 300 µg/mL except for Cu2+ doped HSNs which were cytotoxic even at ~10 µg/mL.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,159,ASO candidate from PMID 37920238,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,B,Materials and methods > Lateral i.c.v. catheter and reservoir implantation through new anchoring system; paragraph 37,1164,Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model.,37920238,PMC10618110,10.1016/j.omtm.2023.101122,https://pubmed.ncbi.nlm.nih.gov/37920238/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Animals that received high doses of the test oligonucleotide (i.e., four times the baseline dose) showed EEG abnormalities, with sharp spikes and waves consistent with seizures (Figure 4B), followed by tonic-clonic movements (Figure 4C).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,161,wireframe DNA origami NANP,DNA nanostructure,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Abstract; paragraph 1,2195,Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice.,37040258,PMC10189729manuscript-id: NIHMS1894368,10.1021/acsabm.3c00155,https://pubmed.ncbi.nlm.nih.gov/37040258/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We assayed liver and kidney biochemistry after administration of PB84 and observed no phenotype for the following biomarkers for toxicity: alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, total serum protein, albumin, globulin, glucose, and bilirubin (Figure 2c).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,162,wireframe DNA origami NANP,DNA nanostructure,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Abstract; paragraph 1,2198,Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice.,36909507,PMC10002694,10.1101/2023.02.25.530026,https://pubmed.ncbi.nlm.nih.gov/36909507/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We assayed liver and kidney biochemistry after administration of PB84 and observed no phenotype for the following biomarkers for toxicity: alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, total serum protein, albumin, globulin, glucose, and bilirubin (Figure 2.C).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,163,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,2. Results > 2.5. Cell Viability; paragraph 14,12521,A Straightforward Method for the Development of Positively Charged Gold Nanoparticle-Based Vectors for Effective siRNA Delivery.,37110552,PMC10144622,10.3390/molecules28083318,https://pubmed.ncbi.nlm.nih.gov/37110552/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Neither CPP-AuNPs nor siRNA/CPP-AuNPs samples showed elevated cytotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,165,SLN360,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 52,1486,"Preclinical Toxicological Assessment of A Novel siRNA, SLN360, Targeting Elevated Lipoprotein (a) in Cardiovascular Disease.",35737426,PMC9516055,10.1093/toxsci/kfac067,https://pubmed.ncbi.nlm.nih.gov/35737426/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In rat and nonhuman primate 29-day toxicology studies, SLN360 was well tolerated at all doses.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,166,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,"Results and discussion > Characterization of LHHK LNPs for morphology, toxicity, serum stability, and hemolytic assay; paragraph 33",1613,Development of amino acid-modified biodegradable lipid nanoparticles for siRNA delivery.,36191773,PMC10695009manuscript-id: NIHMS1944143,10.1016/j.actbio.2022.09.065,https://pubmed.ncbi.nlm.nih.gov/36191773/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The cytotoxicity of LHHK LNPs increased with the higher dose, however higher doses of LHHK LNPs were less cytotoxic compared to Lipofectamine-2000 at some extent (Fig. 5B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,167,inotersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety and tolerability; paragraph 28,1616,Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update.,35908242,PMC9618524,10.1007/s00415-022-11276-8,https://pubmed.ncbi.nlm.nih.gov/35908242/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,169,RAW264; cck8,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and discussion > In vitro inhibition of siTNFα; paragraph 21,4065,Hydrogel-metal-organic-framework hybrids mediated efficient oral delivery of siRNA for the treatment of ulcerative colitis.,36064365,PMC9446571,10.1186/s12951-022-01603-6,https://pubmed.ncbi.nlm.nih.gov/36064365/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Results in Fig. 4a demonstrated that there was no cytotoxicity for different particles.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,170,SKOV3,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 36,4105,Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles.,34382360,PMC11468224,10.1002/adhm.202101202,https://pubmed.ncbi.nlm.nih.gov/34382360/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In SKOV3 cells, liposomes showed a dose‐dependent decrease in cell viability whereas this effect was not observed for hybrids (1:100 and 1:50) indicating increased biocompatibility of hybrids as compared to liposomes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,172,RTR5001,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,4. Discussion; paragraph 49,1463,"Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Göttingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases.",34575518,PMC8470776,10.3390/pharmaceutics13091442,https://pubmed.ncbi.nlm.nih.gov/34575518/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"All animals survived up to the scheduled humane killing, and RTR5001 was clinically well-tolerated at 20 mg/kg/dose.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,173,casimersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 40,1639,"Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial.",34105177,PMC9290993,10.1002/mus.27347,https://pubmed.ncbi.nlm.nih.gov/34105177/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There were no deaths, dose reductions, abnormalities in laboratory parameters or vital signs, or casimersen‐related serious AEs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,174,HepG2; LO2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Cytotoxicity tests; paragraph 28,1641,cRGD peptide-conjugated polyethylenimine-based lipid nanoparticle for intracellular delivery of siRNA in hepatocarcinoma therapy.,34042551,PMC8168781,10.1080/10717544.2021.1928794,https://pubmed.ncbi.nlm.nih.gov/34042551/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There were no obvious histological differences between the major organs including heart, liver, spleen, lungs, and kidney of cRGD-NP/S, cRGD-PSH-NP/S, and saline-treated mice (Figure 8).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,175,Nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 36,1643,Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.,33899154,PMC8563549,10.1007/s00415-021-10569-8,https://pubmed.ncbi.nlm.nih.gov/33899154/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Analysis of mean liver enzyme levels revealed no relevant changes during treatment.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,176,Foxp3,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,2257,Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii.,33801683,PMC8037512,10.3390/ijms22073470,https://pubmed.ncbi.nlm.nih.gov/33801683/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,accounted for more than 90%,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,177,Revusiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,1430,"Nonclinical Safety Profile of Revusiran, a 1st-Generation GalNAc-siRNA Conjugate for Treatment of Hereditary Transthyretin-Mediated Amyloidosis.",31821125,PMC6987735,10.1089/nat.2019.0796,https://pubmed.ncbi.nlm.nih.gov/31821125/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The no observed adverse effect level (NOAEL) in rats was 30 mg/kg based on reversible microscopic changes in liver,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,178,Stk25,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 23,2784,Targeted Delivery of Stk25 Antisense Oligonucleotides to Hepatocytes Protects Mice Against Nonalcoholic Fatty Liver Disease.,30576769,PMC6411916,10.1016/j.jcmgh.2018.12.004,https://pubmed.ncbi.nlm.nih.gov/30576769/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,remained within normal reference values in mice treated with GalNAc-Stk25 ASO,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,179,Huh7; MCF7; nanoparticles43,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 27,4207,Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice.,31676815,PMC6825139,10.1038/s41598-019-52142-4,https://pubmed.ncbi.nlm.nih.gov/31676815/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,induced neither hepatic nor renal toxicities,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,180,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 39,2060,Acute hepatotoxicity of 2' fluoro-modified 5-10-5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins.,29390093,PMC5861398,10.1093/nar/gky060,https://pubmed.ncbi.nlm.nih.gov/29390093/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Significant elevations in ALT (717 U/L) and AST (853 U/L) were observed,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,181,radavirsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Abstract > Results; paragraph 3,2230,"Safety, tolerability, and pharmacokinetics of radavirsen (AVI-7100), an antisense oligonucleotide targeting influenza a M1/M2 translation.",28929521,PMC5736848,10.1111/bcp.13405,https://pubmed.ncbi.nlm.nih.gov/28929521/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,182,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and Discussion > Cytotoxicity; paragraph 5,2787,Saponins as Natural Adjuvant for Antisense Morpholino Oligonucleotides Delivery In Vitro and in mdx Mice.,29858054,PMC5992344,10.1016/j.omtn.2018.02.004,https://pubmed.ncbi.nlm.nih.gov/29858054/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No signs of abnormal behavior or change in body weight and overall condition were observed during treatment with any saponin/PMO polyplexes,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,183,RTR3649; RTR5001; RTR4955,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 65,2324,From the Cover: The Minipig is a Suitable Non-Rodent Model in the Safety Assessment of Single Stranded Oligonucleotides.,28123102,PMC5414856,10.1093/toxsci/kfx025,https://pubmed.ncbi.nlm.nih.gov/28123102/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In the liver, minimal single cell necrosis was observed in 1 of 3 minipigs dosed at 20 mg/kg",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,184,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,4234,Polyquaternium-mediated delivery of morpholino oligonucleotides for exon-skipping in vitro and in mdx mice.,28633548,PMC8241187,10.1080/10717544.2017.1337827,https://pubmed.ncbi.nlm.nih.gov/28633548/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No signs of abnormal behavior or change in body weight and overall condition were observed during systemic treatment with PQ-formulated PMO,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,185,TLR3; TLR7; TLR8,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 33,2327,Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse Model.,26444021,PMC5058343manuscript-id: NIHMS820714,10.3233/JHD-150163,https://pubmed.ncbi.nlm.nih.gov/26444021/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,siRNA infusion did not change the number of DARPP32-positive neurons.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,186,hDysE50,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and discussion > PMO delivery in C2C12 myoblast cell lines expressing GFP/hDysE50; paragraph 17,2812,Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice.,26366082,PMC4562748,10.2147/IJN.S89910,https://pubmed.ncbi.nlm.nih.gov/26366082/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,showed cell viability over 75%,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,187,drisapersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,3. Results > 3.2. Safety results; paragraph 15,2328,Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial.,24321374,PMC4145871manuscript-id: NIHMS592631,10.1016/j.nmd.2013.09.004,https://pubmed.ncbi.nlm.nih.gov/24321374/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No hepatic toxicity, thrombocytopenia, or coagulation abnormalities were reported.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,188,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,4259,Evaluation of Tris[2-(acryloyloxy)ethyl]isocyanurate cross-linked polyethylenimine as antisense morpholino oligomer delivery vehicle in cell culture and dystrophic mdx mice.,24405395,PMC4028087,10.1089/hum.2013.156,https://pubmed.ncbi.nlm.nih.gov/24405395/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Improved transfection efficiency and lower toxicity indicate the potential of the biodegradable PEA polymers as safe and efficient PMO delivery vectors,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,189,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 38,4268,Albumin-based nanoconjugates for targeted delivery of therapeutic oligonucleotides.,23876758,PMC3810404manuscript-id: NIHMS502785,10.1016/j.biomaterials.2013.06.066,https://pubmed.ncbi.nlm.nih.gov/23876758/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,the viability of the cells treated with up to 800 nM equivalent oligonucleotides in nanoconjugates were over 90% of the control cells,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,190,Inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,4. Discussion; paragraph 28,10925,"Efficacy of Alirocumab, Evolocumab, and Inclisiran in Patients with Hypercholesterolemia at Increased Cardiovascular Risk.",39064553,PMC11278919,10.3390/medicina60071124,https://pubmed.ncbi.nlm.nih.gov/39064553/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 39064553; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,192,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > Safety; paragraph 23,1629,"Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial.",34788571,PMC8817703,10.1089/nat.2021.0043,https://pubmed.ncbi.nlm.nih.gov/34788571/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There was no evidence of serious kidney toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,193,MKK4,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 52,1152,Dual targeted gene delivery strategy mediated by GalNAc-modified lipid nanoparticles enhances liver regeneration through specific knockdown of MKK4.,41970250,PMC13067123,10.1016/j.mtbio.2026.103059,https://pubmed.ncbi.nlm.nih.gov/41970250/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,both LNP-siMKK4 and GalNAc-LNP-siMKK4 induced less than 5% of hemolysis rate,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,194,MC3-based,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Tolerability and safety profiles; paragraph 24,1196,Efficiency and safety of five different agents for in vivo delivery of novel bioengineered RNAi molecules.,41907143,PMC13021479,10.3389/fmolb.2026.1785592,https://pubmed.ncbi.nlm.nih.gov/41907143/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,MC3-based LNP-BioRNA treatment led to an 8% decrease in body weights and obvious hepatosplenomegaly,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,196,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and discussion > In vitro anti-fibrotic effect validation of ASO and characterization of ZMO-E5-NPs-ASO properties; paragraph 38,1511,Freezing shock monocytes deliver antisense oligonucleotides via liposomes for the treatment of idiopathic pulmonary fibrosis.,41810474,PMC12925264,10.1016/j.ajps.2026.101128,https://pubmed.ncbi.nlm.nih.gov/41810474/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,did not show significant cytotoxicity,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,197,Gb3S; MC3-containing; Gb3,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Conclusions; paragraph 92,4532,Nanomedicines for DNA and interference RNA co-delivery: Combined gene therapy for Fabry disease.,42170556,PMC13187621,10.1016/j.ijpx.2026.100555,https://pubmed.ncbi.nlm.nih.gov/42170556/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C as borderline: PMID 42170556; curator counted hepatic/hepatotoxicity for Gb3S; MC3-containing; Gb3 despite v2 exclusion. Low-confidence override; v2 note was: ungrounded: proposed viability result quote is not a verbatim span in the loaded passage; available text only states methods/safety summary, insufficient for accepted pr?",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,199,FN1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 44,6205,Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy.,41732388,PMC12925212,10.1016/j.mtbio.2026.102877,https://pubmed.ncbi.nlm.nih.gov/41732388/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Serum biochemistry further showed no significant hepatic or renal toxicity in treated mice,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,202,si097-DV29PG5; si061-DV27PG5,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 30,1477,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen.",40385635,PMC12083919,10.1016/j.omtn.2025.102542,https://pubmed.ncbi.nlm.nih.gov/40385635/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"si097s-DV29PG5, si098-DV29PG5, and Zilebesiran had no effect on blood ALT, AST, or urea levels",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,203,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,3. Results and Discussion > 3.2. Cytotoxicity of LNP-siN.C./siTNF-α and LNP-siN.C./siTNF-α-HCQ; paragraph 26,1551,Innovative Lipid Nanoparticles Co-Delivering Hydroxychloroquine and siRNA for Enhanced Rheumatoid Arthritis Therapy.,39861693,PMC11769357,10.3390/pharmaceutics17010045,https://pubmed.ncbi.nlm.nih.gov/39861693/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,blood biochemical analysis and H&E staining results showed that LNP-siTNF-α-HCQ did not damage blood cells and reduce liver and kidney functions,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,204,AS456; IC50; TRL7,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,3. Discussion; paragraph 24,1788,Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.,41373822,PMC12692593,10.3390/ijms262311675,https://pubmed.ncbi.nlm.nih.gov/41373822/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"siRNA 30 induced elevated expression of multiple ISGs, including IFIT1, OAS1, and ISG20",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,205,RAW264; HepG2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and discussion > Cell viability; paragraph 39,1825,"Self-degradable ""gemini-like"" ionizable lipid-mediated delivery of siRNA for subcellular-specific gene therapy of hepatic diseases.",40654340,PMC12254858,10.1016/j.apsb.2025.04.003,https://pubmed.ncbi.nlm.nih.gov/40654340/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,both unmodified and modified-mannose MA/DC/MH_LNPs maintained cell viability close to 100% across the tested concentration range,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,207,STAT3-targeted,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Abstract; paragraph 2,2155,Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer.,40882634,PMC12404672manuscript-id: NIHMS2102076embargo-date: 2026/08/28,10.1016/j.ccell.2025.07.015,https://pubmed.ncbi.nlm.nih.gov/40882634/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,CS3D has low toxicity and modulation of immune parameters is associated with anti-tumor activity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,208,Tofersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,neurotoxicity,B,Discussion; paragraph 30,2347,Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis.,40017137,PMC12060635,10.1002/mus.28372,https://pubmed.ncbi.nlm.nih.gov/40017137/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Ten participants (approximately 7% of tofersen 100‐mg–treated trial participants) experienced a total of 12 serious neurologic AEs,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,209,givosiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,2503,Efficacy and safety of givosiran in Japanese patients with acute hepatic porphyria: clinical findings from an expanded access study.,40312531,PMC12045942,10.1038/s41598-025-99526-3,https://pubmed.ncbi.nlm.nih.gov/40312531/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,All TEAEs were nonserious and mild or moderate in severity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,210,fitusiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Integrated safety analysis: AEs; paragraph 26,2522,Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study.,40053895,PMC12824673,10.1182/blood.2024027008,https://pubmed.ncbi.nlm.nih.gov/40053895/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Integrated safety analyses of participants receiving AT-DR (n = 286) demonstrated that AT-DR was well tolerated.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,212,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Conclusion; paragraph 65,3595,Peptide dendrimer and hyaluronic acid modified nanovesicles for ocular delivery of timolol maleate and siRNA.,40681573,PMC12274417,10.1038/s41598-025-10960-9,https://pubmed.ncbi.nlm.nih.gov/40681573/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Safety was confirmed via histopathological and ocular irritation assessments.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,213,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and Discussion > In Vivo GFP-pDNA Delivery by TP-SL@PB; paragraph 46,3614,Reprogramming Immunodeficiency in Lung Metastases via PD-L1 siRNA Delivery and Antigen Capture of Nanosponge-Mediated Dendritic Cell Modulation.,40616527,PMC12269356,10.1021/acsnano.5c05395,https://pubmed.ncbi.nlm.nih.gov/40616527/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40616527; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,214,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and Discussion > Cell uptake and toxicity of siRNA@NP@ND in vitro; paragraph 12,3626,A novel ultrasound-responsive cluster bomb system for efficient siRNA delivery in brain.,40582054,PMC12268195,10.1016/j.ultsonch.2025.107446,https://pubmed.ncbi.nlm.nih.gov/40582054/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,without causing significant immune or inflammatory responses. The minor intracranial hemorrhage resulting from this process was also shown to be recoverable.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,215,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and discussion > Anti-metastasis and in vivo biosafety evaluation; paragraph 28,3640,An immune activator encapsulating PD-L1 siRNA for augmented immune checkpoint blockade immunotherapy through Zn(2+) overload triggered pyroptosis.,40524159,PMC12168320,10.1186/s12951-025-03521-9,https://pubmed.ncbi.nlm.nih.gov/40524159/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,there was no significant difference in the serum biochemical indices between the nanoparticles group and Control group,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,216,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results and Discussion > Enhanced Cellular Uptake And Neurospecificity of Targeted Polyplexes; paragraph 14,3690,Engineered Chitosan-Derived Nanocarrier for Efficient siRNA Delivery to Peripheral and Central Neurons.,40364633,PMC12147987,10.1002/adhm.202500107,https://pubmed.ncbi.nlm.nih.gov/40364633/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"These polyplexes demonstrate suitable physicochemical properties, biocompatibility, and no adverse effects on neuronal electrophysiology.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,218,APP36; Iba1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 46,7646,SCAD: A modular platform for efficient delivery of duplex RNA to the CNS and beyond.,41323796,PMC12663631,10.1016/j.omtn.2025.102757,https://pubmed.ncbi.nlm.nih.gov/41323796/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Laboratory assessments including complete blood count, serum chemistry, and protein levels in the CSF showed no abnormalities",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,219,Loop3,aptamer,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,Discussion; paragraph 48,9397,Novel Aptamers Targeting Sclerostin Loop3 Improve Skeletal and Muscle Properties Without Adverse Cardiovascular Effects in Orchiectomized Mice.,40464222,PMC12134771,10.1002/jcsm.13831,https://pubmed.ncbi.nlm.nih.gov/40464222/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No lesions or pathological changes were observed in the heart, aortic roots, liver, spleen, lungs or kidneys.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,224,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,3. Discussion > 3.1. Descriptive Analysis; paragraph 18,2348,Safety of Inclisiran: A Disproportionality Analysis from the EudraVigilance Database.,39459005,PMC11511047,10.3390/ph17101365,https://pubmed.ncbi.nlm.nih.gov/39459005/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In our study, 3.5% of the inclisiran ICSRs reported an ADR related to changes in liver function parameters",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,228,HSP47,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 37,1458,"Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with hepatic impairment.",37654022,PMC10582666,10.1111/cts.13581,https://pubmed.ncbi.nlm.nih.gov/37654022/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Adverse events were reported by two of eight, four of eight, and three of eight participants with mild, moderate, or severe HI, respectively; none were reported in the normal‐matched group.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,229,inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,Results > Safety outcomes; paragraph 13,2676,"Efficacy and safety of inclisiran in patients with cerebrovascular disease: ORION-9, ORION-10, and ORION-11.",37252442,PMC10209488,10.1016/j.ajpc.2023.100503,https://pubmed.ncbi.nlm.nih.gov/37252442/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Treatment-emergent adverse events (TEAEs) and TEAEs at the injection site, mostly mild, were more frequent with inclisiran versus placebo (82.7% vs 70.7% and 3.6% vs 0%, respectively).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,230,PF4,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Abstract; paragraph 1,2680,"Platelet Activation by Antisense Oligonucleotides (ASOs) in the Göttingen Minipig, including an Evaluation of Glycoprotein VI (GPVI) and Platelet Factor 4 (PF4) Ontogeny.",37111598,PMC10143489,10.3390/pharmaceutics15041112,https://pubmed.ncbi.nlm.nih.gov/37111598/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"PS ASOs bind to platelet collagen receptor GPVI and directly activate minipig platelets in vitro, mirroring the findings in human blood samples.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,231,lumasiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 35,2701,Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial.,35913563,PMC9925547,10.1007/s00467-022-05684-1,https://pubmed.ncbi.nlm.nih.gov/35913563/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,235,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > PS- and ME/PS- modified oligonucleotides decrease platelet concentration in vitro; paragraph 29,2755,Antisense oligonucleotides and nucleic acids generate hypersensitive platelets.,33540294,PMC8264460manuscript-id: NIHMS1711667,10.1016/j.thromres.2021.01.006,https://pubmed.ncbi.nlm.nih.gov/33540294/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,We observed a significant decrease in platelet concentrations following incubation with 16 μM PS- or ME/PS-ASO and an even more significant decrease after platelets were exposed to a higher dose (24 μM) of oligonucleotide (Fig. 3A).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,237,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,4. Discussion > 4.2. Supplemented Transfection Medium Stabilizes Nanocomplexes but Harms Human Respiratory Epithelial Cells; paragraph 34,2768,Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells.,32260534,PMC7226018,10.3390/biom10040553,https://pubmed.ncbi.nlm.nih.gov/32260534/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The test showed that CS–ASO nanocomplexes did not have a significant effect on the viability of the cells, while Lipofectamine-containing systems displayed highly significant cytotoxicity (Figure 6).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,238,revusiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,DISCUSSION; paragraph 57,2105,Safety evaluation of 2'-deoxy-2'-fluoro nucleotides in GalNAc-siRNA conjugates.,30820542,PMC6468299,10.1093/nar/gkz140,https://pubmed.ncbi.nlm.nih.gov/30820542/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Modest effects on cell viability and mitochondrial DNA were observed in vitro in a subset of cell types at high concentrations of 2′-F-nucleosides, typically not attained in vivo.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,239,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Materials and Methods > AON administration; FIG. 1. caption,2116,Intracerebroventricular Administration of a 2'-O-Methyl Phosphorothioate Antisense Oligonucleotide Results in Activation of the Innate Immune System in Mouse Brain.,29565739,PMC5899290,10.1089/nat.2017.0705,https://pubmed.ncbi.nlm.nih.gov/29565739/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"A significant upregulation of immune system associated genes was observed in brains of AON treated mice, with the striatum showing largest transcriptional changes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,240,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 36,2322,The Effects of 2'-O-Methoxyethyl Containing Antisense Oligonucleotides on Platelets in Human Clinical Trials.,28145801,PMC5467133,10.1089/nat.2016.0650,https://pubmed.ncbi.nlm.nih.gov/28145801/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,This analysis showed that there is no class generic effect on platelet numbers and no incidence of confirmed platelet levels below 50 K/μL in subjects treated with 2′MOE ASOs.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,241,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 26,2237,Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.,27357629,PMC5112040,10.1038/mt.2016.136,https://pubmed.ncbi.nlm.nih.gov/27357629/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,242,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Discussion; paragraph 21,12119,Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain.,27504598,PMC5023396,10.1038/mtna.2016.50,https://pubmed.ncbi.nlm.nih.gov/27504598/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,243,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,2329,Hepatotoxic potential of therapeutic oligonucleotides can be predicted from their sequence and modification pattern.,23952551,PMC3760025,10.1089/nat.2013.0436,https://pubmed.ncbi.nlm.nih.gov/23952551/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Dose-dependent hepatic changes associated with hepatocyte necrosis and increases in serum alanine-aminotransferase levels have been observed after treatment with certain oligonucleotides.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,244,nusinersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,A,Results; paragraph 15,2611,Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study.,38361750,PMC10864329,10.1016/j.lanepe.2024.100862,https://pubmed.ncbi.nlm.nih.gov/38361750/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No new safety signals were identified.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,245,SPC5001,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1029,Predicting nucleic acid drug-induced nephrotoxicity using a 3D human renal proximal tubule spheroid model.,41500580,,10.2131/jts.51.75,https://pubmed.ncbi.nlm.nih.gov/41500580/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Significant ATP depletion was observed only after prolonged exposure to SPC5001, a nephrotoxic antisense oligonucleotide.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,246,ApoB11; ApoB11-conjugated,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1033,"Peptide-mediated delivery of an α-synuclein-targeting antisense oligonucleotide: Pharmacokinetics, safety, and central nervous system efficacy in a synucleinopathy model.",42172871,,10.1016/j.dmd.2026.100304,https://pubmed.ncbi.nlm.nih.gov/42172871/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Acute and subacute toxicity studies revealed no systemic toxicity at the highest nonlethal dose (32 mg/kg).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,247,SMN2; Nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1064,"A prospective, multi-center, observational study of the safety, tolerability and effectiveness of Nusinersen in adult patients with spinal muscular atrophy.",41813449,,10.1016/j.nmd.2025.106256,https://pubmed.ncbi.nlm.nih.gov/41813449/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No new safety effects were identified.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,248,LRP4; NCT05070858; cemdisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1150,"Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial.",42030965,,10.1016/S0140-6736(26)00690-2,https://pubmed.ncbi.nlm.nih.gov/42030965/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,249,RyR2; Cy5-labeled; RyR2-targeting,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1151,Imaging and safety profiling of inhaled siRNA RyR2 in human respiratory models.,41984094,,10.1007/s00204-026-04370-7,https://pubmed.ncbi.nlm.nih.gov/41984094/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No cytotoxicity was observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,250,PCSK9; Inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,PubMed abstract,1217,Muscle Adverse Events Associated With Inclisiran: Data Mining of FAERS Database and Mendelian Randomization Analysis.,41289434,,10.1097/FJC.0000000000001778,https://pubmed.ncbi.nlm.nih.gov/41289434/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Among 4685 adverse event reports of inclisiran, 523 MAEs reports were found.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,251,patisiran; givosiran; vutrisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1218,Class-Specific Adverse Events of Patients Treated with Small Interfering RNA Therapeutics: A Disproportionality Analysis of the United States Food and Drug Administration Adverse Event Reporting System Database Based on the MY FAERS Platform.,41274662,,10.1177/21593337251391029,https://pubmed.ncbi.nlm.nih.gov/41274662/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,inclisiran demonstrated strong hepatic toxicity signals,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,253,RGLS4326,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1472,"Pharmacokinetics, Safety, and Tolerability of Anti-miR-17 Oligonucleotide RGLS4326 in Healthy Adult Subjects.",42132413,,10.1002/jcph.70207,https://pubmed.ncbi.nlm.nih.gov/42132413/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,RGLS4326 was generally well tolerated,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,254,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1726,Facilitating siRNA delivery into mammalian cells via the LDL receptor.,41956189,,10.1016/j.ijbiomac.2026.151876,https://pubmed.ncbi.nlm.nih.gov/41956189/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 41956189; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,258,PEG6000,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3272,Hemocompatibility of Carbosilane Dendrimers as a Therapeutic siRNA Delivery System across Blood-Brain Barrier.,41664462,,10.1021/acsami.5c12952,https://pubmed.ncbi.nlm.nih.gov/41664462/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,both formulations were nonhemolytic across all concentrations,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,259,Cy5-siRNA; HepG2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3312,"""Zip-to-Cytosol"": Glutathione-Cleavable Fluorinated Polyplexes Deliver siRNA at Single-Digit Nanomolar Dose with >90% Gene Silencing.",41518301,,10.1021/acs.bioconjchem.5c00554,https://pubmed.ncbi.nlm.nih.gov/41518301/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,without detectable hemolysis or cytotoxicity,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,260,PEG2000,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3376,Novel vector for efficient siRNA delivery to lymphoblasts and melanoma based on genipin-spermine nanocarriers protected with hybrid erythrocyte membrane coating.,41076799,,10.1016/j.bioadv.2025.214537,https://pubmed.ncbi.nlm.nih.gov/41076799/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 41076799; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,262,CCL2; MMP9,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,5189,Smart Nanodelivery for Eye-Brain Disorders: Synergistic CCL2 Neutralization and MMP9 Silencing Reverse Anxiety in High Myopia.,42007960,,10.1002/smll.202512276,https://pubmed.ncbi.nlm.nih.gov/42007960/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 42007960; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,264,nusinersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,PubMed abstract,12078,Adverse events of nusinersen: a real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database.,39690144,,10.1080/14740338.2024.2443796,https://pubmed.ncbi.nlm.nih.gov/39690144/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Nusinersen-induced adverse events were observed,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,265,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,8,Toxicity of Antisense Oligonucleotides is Determined by the Synergistic Interplay of Chemical Modifications and Nucleotide Sequences,41078095,,10.1002/cbic.202500584,https://pubmed.ncbi.nlm.nih.gov/41078095/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,ASO toxicity is strongly influenced,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,266,PNPLA3; rs738409; PNPLA3I148M,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1048,Use of a Transgenic Human PNPLA3(I148M) Knock-in Mouse for Translational Safety Evaluations of siRNA Therapeutics.,40899091,,10.1177/21593337251375804,https://pubmed.ncbi.nlm.nih.gov/40899091/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,liver enzyme and histopathology changes,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,267,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract sentence 5,1077,Proceedings of the 2024 Classic Examples in Toxicologic Pathology XXXI.,41457341,,10.1177/01926233251404016,https://pubmed.ncbi.nlm.nih.gov/41457341/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Accept C as borderline: PMID 41457341; curator counted hepatic/hepatotoxicity for unspecified siRNA despite v2 exclusion. Low-confidence override; v2 note was: Proceedings/seminar summary mentions a siRNA hepatotoxicity case but is not a primary toxicity study with sufficient product-level grounding.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,268,Atp5o,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1108,"Hepatotoxicity Reduction Profiles of Antisense Oligonucleotides Containing Amido-Bridged Nucleic Acid and 2'-O,4'-C-Spirocyclopropylene Bridged Nucleic Acid.",40134366,,10.1089/nat.2024.0047,https://pubmed.ncbi.nlm.nih.gov/40134366/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,significantly reduce hepatotoxicity in mice,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,270,SPL84,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1133,"A phase I study assessing the safety and tolerability of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T.",39500647,,10.1016/j.jcf.2024.10.004,https://pubmed.ncbi.nlm.nih.gov/39500647/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,SPL84 was safe and well-tolerated,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,271,NS102; ED50,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1425,Incorporation of a polyamine into lipid nanoparticles increases the endosomal release and transfection of nucleic acids without toxicity.,41167339,,10.1016/j.jconrel.2025.114366,https://pubmed.ncbi.nlm.nih.gov/41167339/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,no significant cytotoxicity or liver toxicity in mice,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,273,TfR1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1468,Self-Assembled Antibody-Oligonucleotide Conjugates for Targeted Delivery of Complementary Antisense Oligonucleotides.,39325927,,10.1002/anie.202415272,https://pubmed.ncbi.nlm.nih.gov/39325927/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,not associated with any toxicity-related morbidity or mortality,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,278,LP5-SeNP; LP1-SeNP,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3484,Peptide-Functionalized Selenium Nanoparticle-Based Effective Delivery System for Src-Targeting siRNA in Triple-Negative Breast Cancer Cells.,41037472,,10.1021/acsabm.5c01486,https://pubmed.ncbi.nlm.nih.gov/41037472/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Cell viability assay revealed that LP5-SeNP and the LP5-SeNP/siRNA complex did not exhibit any cytotoxicity at their experimental concentration.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,283,TUBB3; TUBB3-siRNA; TUBB3-LNPs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3572,TUBB3/DTX LNPs Dry Powder Inhaler and an Efficient Delivery Device for Targeted Therapy of Lung Cancer.,40736337,,10.1021/acsami.5c07808,https://pubmed.ncbi.nlm.nih.gov/40736337/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Experiments with BEAS-2B and H460 cells showed that TUBB3/DTX-LNPs had low cytotoxicity and good biocompatibility with BEAS-2B but strongly inhibited H460 cells.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,288,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3764,Topical delivery of siRNA to psoriatic skin model using high molecular weight chitosan derivatives: In vitro and in vivo studies.,39907973,,10.1007/s13346-025-01800-4,https://pubmed.ncbi.nlm.nih.gov/39907973/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The PEGylated DIPEA-chitosan/siRNA polyplexes demonstrated positive zeta potentials (up to + 11 mV), particle sizes of 100-200 nm, and very low cytotoxicity in keratinocyte and fibroblast cell lines.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,290,miRNA34a; LNA34a; NOTCH1,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,9647,Gemcitabine and miRNA34a mimic codelivery with magnetic nanoparticles enhanced anti-tumor effect against pancreatic cancer.,40306578,,10.1016/j.jconrel.2025.113791,https://pubmed.ncbi.nlm.nih.gov/40306578/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40306578; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,291,siG12Ss; siG12S; KRASG12S,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,9951,A Mannosylated peptidyl lipid CManDA doped into cytidinyl/cationic lipids efficiently delivers siG12Ss to lung cancer in vivo.,40073943,,10.1016/j.jconrel.2025.113624,https://pubmed.ncbi.nlm.nih.gov/40073943/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40073943; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,293,NCT05089084; Plozasiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,10466,Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk.,39225259,,10.1056/NEJMoa2409368,https://pubmed.ncbi.nlm.nih.gov/39225259/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,296,GalNAc3; GalNAc3-conjugated,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1112,Safety and Tolerability of GalNAc(3)-Conjugated Antisense Drugs Compared to the Same-Sequence 2'-O-Methoxyethyl-Modified Antisense Drugs: Results from an Integrated Assessment of Phase 1 Clinical Trial Data.,38227794,,10.1089/nat.2023.0026,https://pubmed.ncbi.nlm.nih.gov/38227794/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, there was a significant increase in mean alanine transaminase levels compared with placebo in the upper dose range of the unconjugated 2'MOE ASO group.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,297,SYT13; Syt13-deficient; Syt13-deficiency,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1453,Preclinical toxicological assessment of amido-bridged nucleic acid-modified antisense oligonucleotides targeting synaptotagmin XIII for intra-abdominal treatment of peritoneal metastasis of gastric cancer.,39192097,,10.1007/s10120-024-01548-9,https://pubmed.ncbi.nlm.nih.gov/39192097/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Weekly intra-abdominal administration of ASO-4733 (125 mg/kg), corresponding to a 50-fold increase of the estimated clinical dose for 4 weeks, was well tolerated by cynomolgus monkeys.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,298,BIIB078; NCT03626012; BIIB078-treated,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1454,"Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study.",39059407,,10.1016/S1474-4422(24)00216-3,https://pubmed.ncbi.nlm.nih.gov/39059407/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,300,SMN2; BPP8-PMO; Cy7,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1582,Efficient systemic CNS delivery of a therapeutic antisense oligonucleotide with a blood-brain barrier-penetrating ApoE-derived peptide.,38749176,,10.1016/j.biopha.2024.116737,https://pubmed.ncbi.nlm.nih.gov/38749176/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The BPP-PMO conjugates significantly increased the level of full-length SMN2 in the patient-derived SMA fibroblasts in a concentration-dependent manner with minimal to no toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,301,Ki67,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1878,"Optimizing lipid nanoparticles for fetal gene delivery in vitro, ex vivo, and aided with machine learning.",39447842,,10.1016/j.jconrel.2024.10.047,https://pubmed.ncbi.nlm.nih.gov/39447842/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The optimized formulations appeared to be safe on ex vivo fetal lungs as indicated by insignificant changes in apoptosis (Caspase-3) and proliferation (Ki67) markers.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,303,PNMVA24,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1926,Poly(N-methyl-N-vinylacetamide): A Strong Alternative to PEG for Lipid-Based Nanocarriers Delivering siRNA.,37994483,,10.1002/adhm.202302712,https://pubmed.ncbi.nlm.nih.gov/37994483/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Safety of DSPE-PNMVA24 is confirmed at the cellular level and in animal models of zebrafish and mice.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,304,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2630,"Safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 524 patients: results from an interim analysis of post-marketing surveillance in Japan.",37649429,,10.1080/00207454.2023.2251662,https://pubmed.ncbi.nlm.nih.gov/37649429/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,AEs occurred in 35.9% of patients (49.0% in infantile-onset SMA and 30.6% in later-onset SMA).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,305,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2634,"Real-world safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 401 Japanese patients: results from an interim analysis of post-marketing surveillance.",35787224,,10.1080/00207454.2022.2095270,https://pubmed.ncbi.nlm.nih.gov/35787224/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The incidence proportion of AEs was 31.7% (37.3% in infantile-onset SMA and 29.1% in later-onset SMA).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,308,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3957,Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study.,38197438,,10.1039/d3nr05738k,https://pubmed.ncbi.nlm.nih.gov/38197438/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Cop+-FND : siRNA potently inhibited the target GAPDH gene with negligible toxicity and sufficient colloidal stability.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,309,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3959,Development and Characterization of Modified Chitosan Lipopolyplex for an Effective siRNA Delivery.,38191947,,10.1208/s12249-023-02728-z,https://pubmed.ncbi.nlm.nih.gov/38191947/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Developed LCAr showed ~4 times less hemolytic potential as compared to the parent polyplexes at the highest siRNA dose.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,311,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,10888,Construction of charge-reversible coordination-crosslinked spherical nucleic acids to deliver dual anti-cancer genes and ferroptosis payloads.,39106627,,10.1016/j.ijbiomac.2024.134515,https://pubmed.ncbi.nlm.nih.gov/39106627/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In vivo data confirmed that the dual gene delivery system successfully targeted CT-26 tumors in tumor-bearing BALB/c mice, and exhibited strong tumor suppression ability, without inducing adverse toxic effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,313,PCSK9; GN3; MC3-LNP,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,11712,Engineering a biomimetic system for hepatocyte-specific RNAi treatment of non-alcoholic fatty liver disease.,37951519,,10.1016/j.actbio.2023.10.038,https://pubmed.ncbi.nlm.nih.gov/37951519/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Having optimized the GalNAc-engineering strategy, insertion orders, and cell membrane source, we obtained the best-performing GalNAc-formulations allowing strong hepatocyte-specific internalization with reduced Kupffer cell capture, resulting in robust gene silencing and less hepatotoxicity when compared with cationic lipid-based GalNAc-formulations.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,315,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,13711,Cysteamine functionalized gold nanoparticles exhibit high efficiency delivery of genetic materials in embryonic stem cells majorly via clathrin mediated endocytosis.,39521158,,10.1016/j.ijpharm.2024.124928,https://pubmed.ncbi.nlm.nih.gov/39521158/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The nanoparticles exhibit no cytotoxicity and can bind to both plasmid DNA (pDNA) as well as small interference RNA (siRNA).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,316,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general toxicity,toxicity,C,PubMed abstract sentence 4,13881,A Metal-Phenolic Network-Enabled Nanoadjuvant to Modulate Immune Responses.,39031853,,10.1002/smll.202401776,https://pubmed.ncbi.nlm.nih.gov/39031853/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Combining the adjuvanticity of aluminum and CpG with RNA interference and MPN coating results in a nanoadjuvant that exhibits greater accumulation in lymph nodes and elicits improved maturation of dendritic cells in comparison to a formulation without siRNA or MPN, and with no observable organ toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,318,NCT03218995,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,PubMed abstract,1600,"Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping.",37207382,,10.1016/j.nmd.2023.03.008,https://pubmed.ncbi.nlm.nih.gov/37207382/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,319,HepG2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1933,Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo.,37871289,,10.1021/acs.biomac.3c00813,https://pubmed.ncbi.nlm.nih.gov/37871289/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,siApoB-Loaded BCP (BCP-siApoB) outperformed lipofectamine counterparts and silenced 93% of ApoB mRNA in HepG2 cells at 50 nM siApoB without inducing cytotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,320,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2304,"Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants.",36415122,,10.1002/cpdd.1197,https://pubmed.ncbi.nlm.nih.gov/36415122/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"All treatment-emergent adverse events (AEs) were mild and resolved by study end, and no AEs or serious AEs resulted in premature study discontinuation or death.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,321,NCT03338816; givosiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2666,Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial.,37479139,,10.1016/j.jhep.2023.06.013,https://pubmed.ncbi.nlm.nih.gov/37479139/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Safety findings demonstrated a continued positive risk/benefit profile for givosiran.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,322,BldA50M50; MixA50; MixD50,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2669,Blended Block Polycation Micelles Enhance Antisense Oligonucleotide Delivery.,37437196,,10.1021/acs.bioconjchem.3c00186,https://pubmed.ncbi.nlm.nih.gov/37437196/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 37437196; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,323,NCT03417102; fitusiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2685,"Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial.",37003287,,10.1016/S0140-6736(23)00284-2,https://pubmed.ncbi.nlm.nih.gov/37003287/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,324,CpG55; rH7HA,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,12177,Developmental and reproductive safety of Advax-CpG55.2™ adjuvanted COVID-19 and influenza vaccines in mice.,37659896,,10.1016/j.vaccine.2023.08.053,https://pubmed.ncbi.nlm.nih.gov/37659896/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No adverse effects of any of the vaccine formulations were observed in the immunized dams or their pups.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,325,pelacarsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,12201,Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects.,36529659,,10.1016/j.jacl.2022.12.001,https://pubmed.ncbi.nlm.nih.gov/36529659/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No serious adverse events or clinically relevant abnormalities in any laboratory parameters were noted.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,327,CL1H6; CL1H6-LNP,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1428,The hydrophobic tail of a pH-sensitive cationic lipid influences siRNA transfection activity and toxicity in human NK cell lines.,34592399,,10.1016/j.ijpharm.2021.121140,https://pubmed.ncbi.nlm.nih.gov/34592399/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"We report here on the development of a siRNA-loaded lipid nanoparticle (LNP) composed of CL1H6 (CL1H6-LNP), an optimized, pH-sensitive cationic lipid, with efficient gene silencing and low cytotoxicity in NK-92 cells.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,328,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1429,"Safety, Tissue Distribution, and Metabolism of LNA-Containing Antisense Oligonucleotides in Rats.",34060347,,10.1177/01926233211011615,https://pubmed.ncbi.nlm.nih.gov/34060347/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,This study reveals different patterns of cell death associated with toxicity in liver (apoptosis and necrosis) and kidney (necrosis only),2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,329,GalNAc3; GalNAc3-MOE; GalNAc3-conjugated,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1465,"Safety, Pharmacokinetic, and Pharmacodynamic Evaluation of a 2'-(2-Methoxyethyl)-D-ribose Antisense Oligonucleotide-Triantenarry N-Acetyl-galactosamine Conjugate that Targets the Human Transmembrane Protease Serine 6.",33431610,,10.1124/jpet.120.000222,https://pubmed.ncbi.nlm.nih.gov/33431610/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Suprapharmacologic doses of ISIS 702843 were well tolerated in NHPs after chronic dosing, and the data indicate that the overall safety profile is very similar to that of the unconjugated 2'-(2-methoxyethyl)-D-ribose (2'-MOE) ASOs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,330,NCT02300233; volanesorsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2754,"Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.",33798466,,10.1016/S2213-8587(21)00046-2,https://pubmed.ncbi.nlm.nih.gov/33798466/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,The most common adverse events were related to tolerability and included injection-site reactions,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,331,TPPS2a; TPPS2a-,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,4126,TNFα siRNA delivery by nanoparticles and photochemical internalization for psoriasis topical therapy.,34437914,,10.1016/j.jconrel.2021.08.039,https://pubmed.ncbi.nlm.nih.gov/34437914/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 34437914; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,333,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1421,Urinary Kidney Biomarker Panel Detects Preclinical Antisense Oligonucleotide-Induced Tubular Toxicity.,33084520,,10.1177/0192623320964391,https://pubmed.ncbi.nlm.nih.gov/33084520/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Dosing 50 mg/kg of the tool ASO resulted in mild proximal tubular pathology and elevations in KIM-1, clusterin, NGAL, and cystatin C.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,334,NCT01737398; Inotersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1422,"Immunogenicity Assessment of Inotersen, a 2'-O-(2-Methoxyethyl) Antisense Oligonucleotide in Animals and Humans: Effect on Pharmacokinetics, Pharmacodynamics, and Safety.",32833564,,10.1089/nat.2020.0867,https://pubmed.ncbi.nlm.nih.gov/32833564/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Finally, no association was observed between IM and toxicity findings (eg, platelet, complement activation, and histopathology findings) in the inotersen 9-month monkey study.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,335,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,12219,Safety of bovine milk derived extracellular vesicles used for delivery of RNA therapeutics in zebrafish and mice.,31877238,,10.1002/jat.3938,https://pubmed.ncbi.nlm.nih.gov/31877238/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"There was a lack of discernable toxicity, mortality and systemic inflammatory or immunological responses in mice following administration of either MNVs or tMNVs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,338,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,C,PubMed abstract,2082,Chronic Toxicity Assessment of 2'-O-Methoxyethyl Antisense Oligonucleotides in Mice.,29708844,,10.1089/nat.2017.0706,https://pubmed.ncbi.nlm.nih.gov/29708844/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The results show that these 2'-MOE ASOs selected for development have consistent behavior between sequences, have tolerability profiles suitable for chronic administration",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,339,Malat1-targeting,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,12059,Role of Computationally Evaluated Target Specificity in the Hepatotoxicity of Gapmer Antisense Oligonucleotides.,30095329,,10.1089/nat.2018.0724,https://pubmed.ncbi.nlm.nih.gov/30095329/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 30095329; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,341,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2083,Highly specific delivery of siRNA to hepatocytes circumvents endothelial cell-mediated lipid nanoparticle-associated toxicity leading to the safe and efficacious decrease in the hepatitis B virus.,28986168,,10.1016/j.jconrel.2017.09.044,https://pubmed.ncbi.nlm.nih.gov/28986168/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,which resulted in a substantial improvement of hepatocyte-specificity and in a dramatic reduction in toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,342,HepG2,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2107,"Impact of Oligonucleotide Structure, Chemistry, and Delivery Method on In Vitro Cytotoxicity.",27923110,,10.1089/nat.2016.0639,https://pubmed.ncbi.nlm.nih.gov/27923110/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"ss PS-ONs were more cytotoxic than double-stranded (ds) PS-ONs, irrespective of the 2'-ribose chemistry, inclusive of the 2'-F modification.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,343,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,genotoxicity,DNA damage response,C,PubMed abstract sentence 2,2232,Locked nucleic acid (LNA): Based single-stranded oligonucleotides are not genotoxic.,28295562,,10.1002/em.22076,https://pubmed.ncbi.nlm.nih.gov/28295562/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,None of the experiments demonstrated a genotoxic effect for the five tested LNA-ONs.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,344,KL4,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,12641,"From Pulmonary Surfactant, Synthetic KL4 Peptide as Effective siRNA Delivery Vector for Pulmonary Delivery.",29121767,,10.1021/acs.molpharmaceut.7b00725,https://pubmed.ncbi.nlm.nih.gov/29121767/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,There was no sign of cytotoxicity or immune response caused by KL4 and KL4/siRNA complexes.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,345,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2801,Toxicological Characterization of Exon Skipping Phosphorodiamidate Morpholino Oligomers (PMOs) in Non-human Primates.,27854228,,10.3233/JND-160157,https://pubmed.ncbi.nlm.nih.gov/27854228/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Findings in these studies were limited to the kidneys, with a common presentation of tubular basophilia, vacuolation, and/or minimal degeneration that was considered non-adverse.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,346,Myo1E,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2084,Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice.,24336348,,10.1093/toxsci/kft278,https://pubmed.ncbi.nlm.nih.gov/24336348/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"After repeated administration, a toxic LNA gapmer (TS-2), but not a non-toxic LNA gapmer (NTS-1), caused hepatocyte necrosis and increased serum alanine aminotransferase levels.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,347,NCT01153932; drisapersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2821,"Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.",25209738,,10.1016/S1474-4422(14)70195-4,https://pubmed.ncbi.nlm.nih.gov/25209738/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The most common adverse events in drisapersen-treated patients were injection-site reactions (14 patients given continuous drisapersen, 15 patients given intermittent drisapersen, and six given placebo) and renal events (13 for continuous drisapersen, 12 for intermittent drisapersen, and seven for placebo), most of which were subclinical proteinuria.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,348,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2823,Local and systemic tolerability of a 2'O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-α delivery by inhalation in mouse and monkey.,24932560,,10.3109/08958378.2014.907587,https://pubmed.ncbi.nlm.nih.gov/24932560/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Systemic bioavailability was minimal, and no systemic toxicity was observed at exposure levels appreciably above pharmacological doses and doses proposed for clinical trials.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,350,STAT3,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2331,Preclinical evaluation of the toxicological effects of a novel constrained ethyl modified antisense compound targeting signal transducer and activator of transcription 3 in mice and cynomolgus monkeys.,23692080,,10.1089/nat.2013.0422,https://pubmed.ncbi.nlm.nih.gov/23692080/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Minimal to slight proximal tubular epithelial cell degeneration and regeneration within the kidney was observed, which had no impact on renal function and showed reversibility at the end of the treatment-free period.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,352,Myd88-deficient; MDA5; LGP2,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,4277,Unique O-methoxyethyl ribose-DNA chimeric oligonucleotide induces an atypical melanoma differentiation-associated gene 5-dependent induction of type I interferon response.,22505629,,10.1124/jpet.112.193789,https://pubmed.ncbi.nlm.nih.gov/22505629/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,followed by acute transaminitis and extensive hepatocyte apoptosis and necrosis at 72 h,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,353,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,4279,Antisense inhibition of coagulation factor XI prolongs APTT without increased bleeding risk in cynomolgus monkeys.,22246038,,10.1182/blood-2011-10-387134,https://pubmed.ncbi.nlm.nih.gov/22246038/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"with no effects on PT, platelets, or increased bleeding following partial tail amputation or gum and skin laceration",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,354,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2066,"Preclinical toxicity and toxicokinetics of GTI-2040, a phosphorothioate oligonucleotide targeting ribonucleotide reductase R2.",20886212,,10.1007/s00280-010-1473-z,https://pubmed.ncbi.nlm.nih.gov/20886212/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In monkeys, there was a dose-related increase in GTI-2040 plasma levels with concomitant increase in complement activation and prolongation of activated partial thromboplastin time.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,355,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,PubMed abstract,2839,"Repeat-dose toxicology evaluation in cynomolgus monkeys of AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) drug for the treatment of duchenne muscular dystrophy.",21540336,,10.1177/1091581811403505,https://pubmed.ncbi.nlm.nih.gov/21540336/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Drug-related microscopic renal effects were dose-dependent, apparently reversible",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,356,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,PubMed abstract,2840,Chemical and mechanistic toxicology evaluation of exon skipping phosphorodiamidate morpholino oligomers in mdx mice.,21540335,,10.1177/1091581811403504,https://pubmed.ncbi.nlm.nih.gov/21540335/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Both AVI-4658 and AVI-4225 were well-tolerated at all doses.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,358,log10; NCT06115993; CTR20232098,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1051,"Safety, pharmacokinetics and antiviral activity of AHB‑137 in healthy volunteers and chronic hepatitis B patients: a phase 1a/1b study.",42176239,,10.1007/s12072-026-11102-7,https://pubmed.ncbi.nlm.nih.gov/42176239/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"No serious adverse events, deaths or discontinuations occurred.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,359,PCSK9; NCT04652726; inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1155,"Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial.",41616799,,10.1016/S2213-8587(25)00351-1,https://pubmed.ncbi.nlm.nih.gov/41616799/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Inclisiran was well tolerated, with a safety profile comparable to studies in adults.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,360,DUX4; iDUX4pA,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1176,Lipid nanoparticle delivery of antisense gapmers attenuates pathology in a mouse model of facioscapulohumeral muscular dystrophy.,42198843,,10.1016/j.ymthe.2026.05.010,https://pubmed.ncbi.nlm.nih.gov/42198843/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 42198843; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,361,PCSK9; inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1179,Comparative effectiveness and safety of inclisiran versus evolocumab and alirocumab: a 180-day real-world study.,42141407,,10.1186/s12872-026-05931-5,https://pubmed.ncbi.nlm.nih.gov/42141407/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,All therapies were well-tolerated with no new safety signals.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,362,AUC0-inf; Zerlasiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1182,"A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants.",42108101,,10.5551/jat.66214,https://pubmed.ncbi.nlm.nih.gov/42108101/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No adverse effects on either the liver or kidney function were observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,363,Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,PubMed abstract,1201,Inclisiran safety and efficacy in real-world clinical practice: results of a retrospective observational investigation.,41860775,,10.2459/JCM.0000000000001852,https://pubmed.ncbi.nlm.nih.gov/41860775/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse effects (5.8%) were mild.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,364,MC3; MC3-based,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1209,Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.,41708903,,10.1007/s13346-026-02076-y,https://pubmed.ncbi.nlm.nih.gov/41708903/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"generally well tolerated, with no adverse effects on body weight or pulmonary function at therapeutic doses",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,365,NCT04014335; RO7434656; sefaxersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1308,A single-arm phase 2 trial of an investigational RNA therapeutic to complement factor B sefaxersen for treatment of IgA nephropathy.,41443406,,10.1016/j.kint.2025.11.017,https://pubmed.ncbi.nlm.nih.gov/41443406/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Transient and reversible alanine amino transferase elevations (3-5X fold upper limit normal) without a change in bilirubin were observed in three individuals,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,368,MC3-LNP,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1375,Mucus-penetrating lipid nanoparticles overcome lung barriers for pulmonary co-delivery of siGSDMD and pDNA-SAP in idiopathic pulmonary fibrosis.,41985596,,10.1016/j.ijpharm.2026.126878,https://pubmed.ncbi.nlm.nih.gov/41985596/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Both in vitro and in vivo studies indicated a favorable safety profile for DAS-LNP.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,369,ABCG2; HCC1937; Ki67,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1392,"cRGD-modified, pH-sensitive liposomes for co-delivery of docetaxel and ABCG2 siRNA enhance therapeutic efficacy in triple-negative breast cancer.",41865608,,10.1016/j.colsurfb.2026.115616,https://pubmed.ncbi.nlm.nih.gov/41865608/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"induced minimal hemoglobin release, with hemolysis rates remaining below safety threshold.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,370,GATHER2; NCT04435366; mm2,aptamer,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1520,Avacincaptad Pegol for Geographic Atrophy Secondary to Age-Related Macular Degeneration: Two-Year Efficacy and Safety Results from the GATHER2 Phase 3 Trial.,41407269,,10.1016/j.ophtha.2025.12.011,https://pubmed.ncbi.nlm.nih.gov/41407269/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,371,NCT04439539; FUW48; log10IU,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1775,Peginterferon alpha-2a add-on to siRNA JNJ-73763989 in untreated patients with HBeAg-positive chronic hepatitis B virus (HBV) infection: the phase 2 REEF-IT study.,41193172,,10.1136/gutjnl-2025-336592,https://pubmed.ncbi.nlm.nih.gov/41193172/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,There were no deaths or serious AEs,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,372,NCT05618379; Nusinersen,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2417,Effectiveness and Safety of Nusinersen Among Adults with 5q-Spinal Muscular Atrophy: A Multicenter Disease Registry in China.,41461996,,10.1007/s12325-025-03475-2,https://pubmed.ncbi.nlm.nih.gov/41461996/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Three participants reported five mild adverse events, none of which were considered related to nusinersen by the investigators.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,376,CORE2-TIMI; NCT05079919; NCT05552326,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,7173,Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk.,41211918,,10.1056/NEJMoa2512761,https://pubmed.ncbi.nlm.nih.gov/41211918/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Elevations in liver-enzyme levels and thrombocytopenia (platelet count, <100,000 per microliter) were more common with the 80-mg dose of olezarsen, and a dose-dependent increase in the hepatic fat fraction was noted.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,377,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1127,Safety and efficacy of KRAS antisense oligonucleotides and RIG-I agonists delivered by extracellular vesicles for pancreatic cancer peritoneal metastasis treatment.,40967408,,10.1016/j.jconrel.2025.114239,https://pubmed.ncbi.nlm.nih.gov/40967408/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"this combination therapy is well-tolerated in non-human primates, with no observable changes in physical condition or behavior, blood parameters, or organ histology.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,378,viltolarsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1274,Safety and efficacy of viltolarsen treatment in patients with Duchenne muscular dystrophy: A retrospective study with 3-year follow-up.,39549635,,10.1016/j.braindev.2024.10.005,https://pubmed.ncbi.nlm.nih.gov/39549635/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Two patients showed significant treatment-related adverse events, namely swelling of the dorsal surface of the right hand due to extravasation of viltolarsen in one patient and axillary lymph node enlargement due to frequent intravenous infusion in another patient.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,379,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1541,"A Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-101, an RNAi Therapeutic Targeting HBV Infection.",40607962,,10.1002/cpdd.1569,https://pubmed.ncbi.nlm.nih.gov/40607962/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,a single dose of HT-101 at 25-800 mg was safe and well tolerated in healthy Chinese volunteers.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,380,GPC3-LPPEI; GPC3-targeting; GPC3,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2097,Research on Anti-tumor Pharmacodynamics of Multi-functional Magnetic Lipid Polymer with Specific Targeted Transmission of siRNA and its Toxicity Evaluation.,41121471,,10.2174/0113816128395585250923122829,https://pubmed.ncbi.nlm.nih.gov/41121471/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 41121471; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,382,PCSK9; NCT05763875; Inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2280,Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial.,40392667,,10.1016/j.jacc.2025.04.049,https://pubmed.ncbi.nlm.nih.gov/40392667/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Inclisiran was well tolerated, with no new safety concerns.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,383,SOX9; MC3-DMA; siSOX9,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2475,"SOX9 siRNA Loaded Lipid Nanoparticles Actively Targeted: Formulation, Delivery, and Antitumor Effect on Colorectal Cancer In Vitro and In Vivo.",40717437,,10.1021/acs.molpharmaceut.5c00272,https://pubmed.ncbi.nlm.nih.gov/40717437/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Furthermore, R-LNPs demonstrated favorable safety in in vivo application.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,384,inclisiran,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,PubMed abstract,2510,Efficacy and safety of inclisiran based on background lipid-lowering treatment.,40242982,,10.1093/eurjpc/zwaf214,https://pubmed.ncbi.nlm.nih.gov/40242982/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40242982; weak/generic or abstract-limited support for general safety/safety/tolerability.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,385,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,3747,Surfactant protein B-derived peptides as endosomal escape enhancers for pulmonary delivery of siRNA.,40010411,,10.1016/j.jconrel.2025.02.067,https://pubmed.ncbi.nlm.nih.gov/40010411/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Moreover, they exhibit enhanced resistance to vibrating mesh nebulization and reduced inflammatory activation of bronchial epithelial cells.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,386,Nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,7632,Real-Time Ultrasound-Guided Intrathecal Delivery of Nusinersen in Adult Patients With Spinal Muscular Atrophy and Complex Spinal Anatomy.,41337773,,,https://pubmed.ncbi.nlm.nih.gov/41337773/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No severe adverse events were observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,388,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,12427,Bone-targeted ultrasound-responsive nanobubbles for siRNA delivery to treat osteoporosis in mice.,39447239,,10.1016/j.bioadv.2024.214078,https://pubmed.ncbi.nlm.nih.gov/39447239/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"No adverse effects were recorded within histological assessments on the liver, kidney, and heart post-treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,389,NCT04971928; AUC0; Bepirovirsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1564,"A Phase 1, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Bepirovirsen in Adults with Hepatic Impairment and Healthy Participants (B-Assured).",39268699,,10.1002/cpdd.1454,https://pubmed.ncbi.nlm.nih.gov/39268699/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse events were mild. Moderate HI did not have a clinically relevant impact on bepirovirsen PK or safety.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,390,NCT05139810,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,1580,Efficacy and Safety of Donidalorsen for Hereditary Angioedema.,38819395,,10.1056/NEJMoa2402478,https://pubmed.ncbi.nlm.nih.gov/38819395/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,391,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1585,A potent bioreducible ionizable lipid nanoparticle enables siRNA delivery for retinal neovascularization inhibition.,38636882,,10.1016/j.ejpb.2024.114296,https://pubmed.ncbi.nlm.nih.gov/38636882/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 38636882; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,392,CDR132L,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,B,PubMed abstract,2619,Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.,38269451,,10.1002/ejhf.3139,https://pubmed.ncbi.nlm.nih.gov/38269451/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C as borderline: PMID 38269451; curator counted general safety/safety/tolerability for CDR132L despite v2 exclusion. Low-confidence override; v2 note was: Trial rationale/design abstract for CDR132L describes planned efficacy and safety assessment and cites prior phase 1b tolerability, but does not report a primary observe?",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,393,caspase3,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,3866,Delivery of SiRNA-PD-L1 by attenuated Salmonella in combination with oxaliplatin in a hepatocellular carcinoma mouse model.,39146787,,10.1016/j.intimp.2024.112892,https://pubmed.ncbi.nlm.nih.gov/39146787/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 39146787; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,394,NCT03672188; log10; elebsiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,10687,VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study.,39389081,,10.1016/S2468-1253(24)00237-1,https://pubmed.ncbi.nlm.nih.gov/39389081/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Most treatment emergent adverse events were grades 1-2. Three (20%) participants in cohort 1, four (27%) in cohort 2, eight (44%) in cohort 3, seven (39%) in cohort 4, six (46%) in cohort 5, and two (40%) in cohort 6 reported treatment-emergent adverse events related to VIR-2218.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,396,Ago2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,safety/tolerability,C,PubMed abstract,1137,"Shorter Is Better: The α-(l)-Threofuranosyl Nucleic Acid Modification Improves Stability, Potency, Safety, and Ago2 Binding and Mitigates Off-Target Effects of Small Interfering RNAs.",37638886,,10.1021/jacs.3c04744,https://pubmed.ncbi.nlm.nih.gov/37638886/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In a rat toxicology study, TNA placed at position 7 of the antisense strand of the siRNA mitigated off-target effects, likely due to the decrease in the thermodynamic binding affinity relative to the 2'-O-methyl residue.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,397,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematological,thrombocytopenia,C,PubMed abstract,2199,The mechanism of thrombocytopenia caused by cholesterol-conjugated antisense oligonucleotides.,36801361,,10.1016/j.tiv.2023.105569,https://pubmed.ncbi.nlm.nih.gov/36801361/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,An increase in the number of large particle-size events with platelet activation was detected in the Chol-ASO-treated group.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,398,Inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2301,Safety and Tolerability of Inclisiran for Treatment of Hypercholesterolemia in 7 Clinical Trials.,38057066,,10.1016/j.jacc.2023.10.007,https://pubmed.ncbi.nlm.nih.gov/38057066/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Kaplan-Meier analyses showed that TEAEs that were serious or led to discontinuation; hepatic, muscle, and kidney events; incident diabetes; and elevations of creatine kinase or creatinine accrued at a comparable rate between groups for up to 1.5 years, with similar trends continuing for inclisiran beyond this period.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,399,NCT03982186,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2303,"Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial.",37442152,,10.1016/S2468-1253(23)00148-6,https://pubmed.ncbi.nlm.nih.gov/37442152/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Ten (2%) of 470 patients had serious adverse events during the treatment phase, and two patients (one each from the JNJ-3989 dual 200 mg group [exercise-related rhabdomyolysis] and the triple group [increase in ALT or AST]) had serious adverse events related to study treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,400,Volanesorsen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2681,Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial.,37100699,,10.1016/j.jacl.2023.03.007,https://pubmed.ncbi.nlm.nih.gov/37100699/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Common adverse events were injection site reactions and platelet count decrease, consistent with previous studies.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,401,PCSK9; NCT03060577; inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2697,Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial.,36620965,,10.1016/S2213-8587(22)00353-9,https://pubmed.ncbi.nlm.nih.gov/36620965/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse events at the injection site were reported in 39 (14%) of 284 patients in the inclisiran-only arm and 12 (14%) of 87 patients in the switching arm.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,402,SPL84,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,12058,"The safety and toxicity profile of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T mutation, supports a Phase 1/2 clinical study.",37799089,,10.1080/17425255.2023.2266361,https://pubmed.ncbi.nlm.nih.gov/37799089/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"There were no preclinical safety findings with SPL84; no related clinical signs, nor any effect on body weight, food consumption, or clinical pathology.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,407,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematological,thrombocytopenia,C,PubMed abstract,2314,Impurity Qualification Toxicology Study for a 2'-O-Methoxyethyl-Modified Antisense Inhibitor in Mice.,31687889,,10.1089/nat.2019.0780,https://pubmed.ncbi.nlm.nih.gov/31687889/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"The expected common class effects were observed at the 30 mg/kg/week dose level in hematology, serum chemistry, and histopathology.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,408,antiPF4,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,2318,"Investigation into the Mechanism(s) That Leads to Platelet Decreases in Cynomolgus Monkeys During Administration of ISIS 104838, a 2'-MOE-Modified Antisense Oligonucleotide.",29846725,,10.1093/toxsci/kfy119,https://pubmed.ncbi.nlm.nih.gov/29846725/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In response to continued dosing, PLT counts were decreased by 50%-90% by day 30 in all monkeys.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,410,SGLT2,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,PubMed abstract,2086,"Pharmacodynamics and subchronic toxicity in mice and monkeys of ISIS 388626, a second-generation antisense oligonucleotide that targets human sodium glucose cotransporter 2.",22915769,,10.1124/jpet.112.197426,https://pubmed.ncbi.nlm.nih.gov/22915769/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,No changes in kidney function were observed.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,411,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2109,Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults.,22704926,,10.1016/j.vaccine.2012.05.074,https://pubmed.ncbi.nlm.nih.gov/22704926/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,412,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,2110,Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age.,22326642,,10.1016/j.vaccine.2012.01.087,https://pubmed.ncbi.nlm.nih.gov/22326642/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,413,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,C,PubMed abstract,2269,Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey.,22709826,,10.1016/j.tox.2012.06.005,https://pubmed.ncbi.nlm.nih.gov/22709826/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,414,Inclisiran,siRNA,PCSK9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,clinical laboratory safety,A,RESULTS > Safety Analysis; paragraph 36,2498,"Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial.",40391436,PMC12180692,10.1161/CIRCULATIONAHA.124.073233,https://pubmed.ncbi.nlm.nih.gov/40391436/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,415,IL-4Ralpha ASO,ASO,IL4RA,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,body weight/general tolerability,C,"RESULTS > IL-4Rα silencing in vivo reverses LV remodeling, reduces cardiac fibrosis, and improves neovascularization in HF.; paragraph 25",9646,CD206(+)IL-4Rα(+) Macrophages Are Drivers of Adverse Cardiac Remodeling in Ischemic Cardiomyopathy.,40308203,PMC12303760manuscript-id: NIHMS2075744,10.1161/CIRCULATIONAHA.124.072411,https://pubmed.ncbi.nlm.nih.gov/40308203/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Body weight was comparable between the mouse groups over the 4 w treatment period (Figure S13A).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,416,Nusinersen,ASO,SMN2,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,adverse event reporting,A,Results > Risk signal detection; paragraph 11,1571,Unveiling the adverse events of Nusinersen in spinal muscular atrophy management based on FAERS database.,39060346,PMC11282055,10.1038/s41598-024-67627-0,https://pubmed.ncbi.nlm.nih.gov/39060346/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,417,Inclisiran,siRNA,PCSK9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,treatment-emergent adverse events,A,Results > Safety; paragraph 23,2632,"Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials.",36550348,PMC11101568,10.1007/s10557-022-07413-0,https://pubmed.ncbi.nlm.nih.gov/36550348/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Proportions of patients with reported treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events were similar between treatment arms, irrespective of PVD status, except for an excess of mild or moderate clinically relevant TEAEs at the injection site with inclisiran.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,418,AVI-6002/AVI-6003 PMOplus,PMOplus,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,clinical safety and pharmacokinetics,B,Abstract; paragraph 1,2822,Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against ebola virus and marburg virus: results of two single-ascending-dose studies.,25155593,PMC4249403,10.1128/AAC.03442-14,https://pubmed.ncbi.nlm.nih.gov/25155593/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,419,phosphorothioate ASO panel,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,neurological,acute neuronal inhibition,A,"Results > Acute inhibition is transient, reversible, and dose-dependent following CNS ASO administration; paragraph 26",1044,Acute neuronal inhibition response caused by phosphorothioate antisense oligonucleotides following local delivery to the central nervous system.,41494985,PMC12865454,10.1093/nar/gkaf1333,https://pubmed.ncbi.nlm.nih.gov/41494985/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Across species, inhibition-like responses peaked ∼3 h post-ASO delivery, reversed within 24 h with no sequelae, and could be quantified using simple neurobehavioral scales.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,420,G5-GalNAc siRNA platform,siRNA,PCSK9/AGT,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,nonclinical toxicology and biodistribution safety,C,Discussion; paragraph 17,1069,Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.,41541269,PMC12800395,10.1016/j.omtn.2025.102801,https://pubmed.ncbi.nlm.nih.gov/41541269/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The no observed adverse effect level was established at 300 mg/kg.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,421,TET3 siRNA lipid nanoparticles,siRNA,TET3,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,hemolysis and cytotoxicity,A,Results > Preparation and characterization of TET3 siRNA@αmp-lipo; paragraph 95,1192,Dual-targeted lipid nanoparticles for TET3 siRNA delivery: nanobiotechnology strategy to remodel tumor immune microenvironment in hepatocellular carcinoma.,41923247,PMC13169958,10.1186/s12951-026-04312-6,https://pubmed.ncbi.nlm.nih.gov/41923247/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In vitro experiments demonstrated the nanoparticles’ excellent biocompatibility, stability, and ability to silence TET3",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,423,CaP-siSlc31a1,siRNA,SLC31A1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results and discussion > Fabrication of CaP-siSlc31a1 for efficient cellular uptake and gene silencing; paragraph 13,1735,Transdermal siRNA delivery via biomineralized nanoparticle-incorporated microneedles modulates cuproptosis-ferroptosis interaction for psoriasis therapy.,41809386,PMC12969650,10.1016/j.mtbio.2026.102991,https://pubmed.ncbi.nlm.nih.gov/41809386/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Even at equivalent siRNA concentrations, CaP-siSlc31a1 maintained over 80% cell viability, indicating excellent biocompatibility.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,424,FW-LP@siIRF5,siRNA,IRF5,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,hematology/clinical chemistry/histology safety,A,Results > In Vivo Biosafety of FW-LP@siIRF5; paragraph 46,1741,Reprogramming Lesional Macrophage Homeostasis via Interferon Regulatory Factor 5 Targeted siRNA Nanoimmunotherapy for Atherosclerosis.,41776767,PMC13001080,10.1021/acsnano.5c18044,https://pubmed.ncbi.nlm.nih.gov/41776767/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"body weight curves (Figure S18), organ histology (Figure A), blood chemistry profiles (Figure B), and hepatic and renal function biomarkers (Figure C) in the treatment group were comparable to those in saline-treated controls, indicating tolerability during prolonged administration.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,425,DCA-JAK13033 siRNA,siRNA,JAK1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic exposure and immunogenicity safety,A,"Results > Intradermal administration of conjugated JAK13033 siRNAs in pigs demonstrates durable skin retention for at least 2 months, minimal systemic exposure, and a favorable safety profile; paragraph 12",1750,Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.,41634015,PMC12976281,10.1038/s41467-026-68993-1,https://pubmed.ncbi.nlm.nih.gov/41634015/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Additionally, blood levels of platelets (thrombocytopenia), white blood cell count (inflammation), alanine aminotransferase (ALT, liver damage), and carbamide (kidney damage) had no significant changes (Fig. 2c).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,426,siRNA nanocarriers/lipoplexes,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results > Cytotoxicity of siRNA nanocarriers; paragraph 24,2428,Pulmonary delivery of siRNA lipoplexes and lipid nanoparticles using a vibrating mesh nebuliser.,41274361,PMC12700850,10.1016/j.ejps.2025.107386,https://pubmed.ncbi.nlm.nih.gov/41274361/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,All other formulations showed cell viability values > 80 % indicating low cytotoxicity (Fig.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,427,DP-EVs/siPD-L1,siRNA,CD274,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic toxicity/histology/body weight,A,Results > In Vivo Antitumor Efficacy Evaluation of DP‐EVs/siPD‐L1; paragraph 28,3228,An Engineered Extracellular Vesicle With Enhanced Tumor and Lymph Nodes Targeting as siRNA Delivery System for Robust Tumor Immunotherapy.,41815210,PMC12972210,10.1002/mco2.70673,https://pubmed.ncbi.nlm.nih.gov/41815210/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Hematoxylin and eosin (H&E) staining of major organs revealed no pathological abnormalities, and all groups showed stable increase of body weight during therapy, suggesting minimal systemic toxicity (Figure S11A,B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,429,TGF-beta siRNA PMNP,siRNA,TGFB1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic/renal,hepatotoxicity and kidney function,A,Results and discussion > Assessment of hepatotoxicity and kidney function; paragraph 15,3262,Polyplex of peptide-mannan and RNA for intranasal delivery of TGF-β siRNA in treatment of pulmonary fibrosis.,41704233,PMC12907503,10.1016/j.bioactmat.2026.02.006,https://pubmed.ncbi.nlm.nih.gov/41704233/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The results collectively suggest that intranasal administration of M8NPs does not induce hepatotoxicity or impair kidney function under the tested conditions.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,430,siRNA polyplexes,siRNA,Raf-1/PD-L1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic toxicity,C,Conclusion.; paragraph 24,3263,An effective tumor-inhibiting siRNA delivery platform.,41691982,PMC13183465manuscript-id: NIHMS2163813,10.1016/j.bbrc.2026.153430,https://pubmed.ncbi.nlm.nih.gov/41691982/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Notably, no toxicity was observed with these systemically delivered siRNA polyplexes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,432,siRNA-loaded CaP-NP/cGM formulation,siRNA,Chordin,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/biocompatibility,A,Results > PLGA NPs are suitable biocompatible nanocarriers for siRNAs delivery in CMSCs; paragraph 53,3276,A smart nanocomposite bioactive ink for controlled siRNA delivery in calvarial mesenchymal stromal cells as a minimally invasive treatment for craniosynostosis.,41647289,PMC12869795,10.1093/rb/rbaf115,https://pubmed.ncbi.nlm.nih.gov/41647289/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The MTT assay showed no significant differences in the viability of cells treated with PLGA NPs for 48 h at all tested concentrations (0.02, 0.04, 0.2, 0.5, 2.5 mg/mL) compared with the untreated controls, indicating that PLGA NPs did not affect cellular metabolism (Figure 5A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,434,siB/QU@L-OL,siRNA,BACE1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,in vivo biosafety/hepatic renal and local nasal toxicity,A,Results and discussion > In vivo biosafety assessment; paragraph 52,3297,Intranasal delivery of Odorranalectin-modified lipid nanoparticles for multi-targeted therapy of Alzheimer's disease.,41560836,PMC12814076,10.1016/j.mtbio.2026.102764,https://pubmed.ncbi.nlm.nih.gov/41560836/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Hemolysis assays further confirmed that siB/QU@L-OL caused no detectable erythrocyte lysis at any of the tested concentrations (Fig. 1K).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,435,curcumin coacervate siRNA formulation,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,hemolysis/blood compatibility,A,Results and Discussion > Curcumin coacervates enrich in the tumor site through tail vein injection; paragraph 31,3316,Curcumin coacervates for supramolecular-interaction-responsive cytosolic siRNA delivery to enhance pyroptosis.,41510156,PMC12775651,10.7150/thno.121865,https://pubmed.ncbi.nlm.nih.gov/41510156/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Blood biochemical analysis showed no significant difference in white blood cells (WBC), RBC, hemoglobin (HGB), and platelets (PLT) (Figures 6C-F).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,436,siRNA@VG-Exos,siRNA,IL6,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic/renal/general safety,histology and serum biochemistry safety,A,Result > In vivo safety assessment of siRNA@VG-Exos; paragraph 31,3325,Endothelial-targeted modification of ginseng-derived exosomes for IL-6 SiRNA delivery ameliorates hepatic ischemia-reperfusion injury.,41491215,PMC12781530,10.1186/s12951-025-03954-2,https://pubmed.ncbi.nlm.nih.gov/41491215/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Serum biochemical markers of renal function (CREA, BUN) and hepatic function (ALT, AST) showed no significant differences compared to the control group (Fig. 9B-E).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,437,LNP-SNORA49 RNA/SOX9 ASO,ASO/RNA mixed context,SOX9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,organ morphology/body weight/cytokine safety,B,Results > Lipid nanoparticle delivery of SNORA49 and ASOs against SOX9 exerts synergistic antitumor effect on HCC tumors; paragraph 25,6668,SNORA49 negatively regulates self-renewal of liver cancer stem cells and hepatocarcinogenesis via suppressing SOX9 transcription.,41565615,PMC12824223,10.1038/s41467-025-66486-1,https://pubmed.ncbi.nlm.nih.gov/41565615/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Compared with control groups, those treated with either empty LNP vectors or LNP-RNAs displayed normal liver, kidney, and spleen morphology, comparable body weight and organ size",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,438,pPB-siRNATRAF6/NMm-pPB-siRNATRAF6,siRNA,TRAF6,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results and discussion > In vitro targeting of inflammatory macrophages and nerve cells; paragraph 11,6682,Spatiotemporal delivery of multifunctional nanozymes for neuroinflammation alleviation via autophagy modulation in spinal cord injury.,41560791,PMC12813177,10.1016/j.mtbio.2025.102734,https://pubmed.ncbi.nlm.nih.gov/41560791/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"CCK-8 assays revealed that these nanoparticles (with PB at 100 μg/mL) did not significantly affect the cell viability in BMDMs and PC12 cells (a common neuronal cell line) over periods of 24, 48, and 72 h (Fig. S6, A and B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,439,pMSNC@ISG15 siRNA,siRNA,ISG15,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,in vivo biocompatibility/clinical chemistry,A,Results > pMSNC@ISG15 siRNA exhibits favorable in vivo biocompatibility and cardiac tissue targeting; paragraph 78,6684,Interferon-stimulated gene 15 small interfering RNA-loaded polarized mesoporous silica nanocarriers remodel the immune microenvironment to ameliorate post-myocardial infarction heart failure.,41560785,PMC12813121,10.1016/j.mtbio.2025.102631,https://pubmed.ncbi.nlm.nih.gov/41560785/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The synthesized pMSNC@ISG15 siRNA nanoparticles effectively suppressed ISG15 expression in cardiac cells, exhibited excellent biocompatibility, and inhibited immune cell activation in vivo.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,440,SANG-siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic toxicity/repeat-dose tolerability,A,Results > Systemic delivery of SANGs is minimally toxic; paragraph 20,6833,Tumor agnostic drug delivery with dynamic nanohydrogels.,41500988,PMC12780282,10.1038/s41467-025-66788-4,https://pubmed.ncbi.nlm.nih.gov/41500988/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,A repeat-dose tolerability study of high-dose SANG-siRNA and co-infused oxaliplatin in rats with advanced colorectal cancer42 produced no mortality or any clinical signs of distress while weights recovered back to baseline by study completion (Supplementary Fig. 20).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,441,cationic/anionic siRNA lipoplexes,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results > Cytotoxicity of cationic and anionic siRNA lipoplexes; paragraph 27,12337,Assessment of anionic siRNA lipoplexes prepared via modified ethanol injection for tumor cell delivery.,41282509,PMC12635908,10.3892/br.2025.2085,https://pubmed.ncbi.nlm.nih.gov/41282509/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Cationic and anionic siRNA lipoplexes were transfected into MCF-7-Luc and HeLa-Luc cells, with viability measured after 48 h.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,442,ISIS 405879,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematological,thrombocytopenia,B,Abstract; paragraph 1,1131,Cellular immune changes during severe antisense oligonucleotide-associated thrombocytopenia in a nonhuman primate model.,40101742,PMC12043408manuscript-id: NIHMS2042395,10.1093/jimmun/vkae055,https://pubmed.ncbi.nlm.nih.gov/40101742/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Seven out of 9 Mauritian origin NHPs developed severe TCP with platelet nadir < 50K/uL as early as after two months of treatment.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,443,LNP TNF-alpha siRNA,siRNA,TNF,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results and Discussion > Characterizing the In Vitro Anti‐Inflammatory Effect of LNP TNF‐α siRNA; paragraph 11,1538,Pulmonary Delivery of siRNA Anti-TNFα-loaded Lipid Nanoparticles for Rapid Recovery in Murine Acute Lung Injury.,40776451,PMC12616584,10.1002/adhm.202500695,https://pubmed.ncbi.nlm.nih.gov/40776451/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Notably, both LNP formulations exhibited no cytotoxicity, even at high concentrations.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,444,siSTAT3 silk sphere formulation,siRNA,STAT3,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,B,Results and Discussion > Analysis of the Gene Silencing Effect Exerted of siRNA Delivered Using H2.1MS1KN and H2.1MS1:MS2KN Spheres; paragraph 47,1829,"Developing the Strategy to Use Silk Spheres for Efficient, Targeted Delivery of Oligonucleotide Therapeutics to Cancer Cells.",40584785,PMC12204100,10.2147/IJN.S519906,https://pubmed.ncbi.nlm.nih.gov/40584785/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Spheres made of H2.1MS1KN and a blend of H2.1MS1 and MS2KN2 silks were not cytotoxic when examined at a wide range of concentrations (Figure 4).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,446,CDs-pDEAEMA/BIRC5 siRNA,siRNA,BIRC5,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cytocompatibility/erythrocompatibility,A,Results and Discussion > Cell Compatibility; paragraph 50,3695,Poly(2-(diethylamino)ethyl methacrylate)-Functionalized Carbon Nanodots as Theranostic Platforms for siRNA Delivery and Survivin Silencing in Triple-Negative Breast Cancer.,40347142,PMC12152932,10.1021/acs.biomac.5c00267,https://pubmed.ncbi.nlm.nih.gov/40347142/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The studies conducted on red blood cells (Figure ) showed that the complexes obtained with the lower ratios (R: 3, 4, 5) were entirely compatible, with erythrolysis levels comparable to those observed when incubating cells in phosphate buffer, values attributable to the stress endured by the cells during operational procedures (e.g., centrifugation, resuspension).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,447,NLP-exosome complex STAT3 siRNA,siRNA,STAT3,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,C,3. Results > 3.1. The Use of NLP-EXOSOME COMPLEX Nanoparticles Results in the Production of Reliable and Efficient Formulations for Delivering siRNA; paragraph 29,9471,Exosome Enveloped by Nano Lipid Particle a New Model for Signal Transducer and Activator of Transcription 3 Silencer Ribonucleic Acid Delivery System to a Glioblastoma Mice Model.,40427146,PMC12109797,10.3390/cancers17101648,https://pubmed.ncbi.nlm.nih.gov/40427146/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The lack of cell damage during transfection suggests that NLP-EXOSOME COMPLEX is also safe for use in the central nervous system (CNS) in vivo, and the similar results seen with parental activity indicate that the degradation of NLP-EXOSOME COMPLEX and release of the complex does not cause toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,448,P-HyOMe-WRAP5:siF3 nanoparticles,siRNA,FADD,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,B,Results and Discussion > FADD Knockdown in Human Cardiomyocytes Using PEGylated pH-Sensitive WRAP5 Nanoparticles at pH 5; paragraph 53,9935,Enhancing WRAP-Based Nanoparticles for Small Interfering Ribonucleic Acid Delivery in pH-Sensitive Environments.,40084851,PMC12132915,10.1002/cmdc.202400885,https://pubmed.ncbi.nlm.nih.gov/40084851/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In contrast, for the 100% P‐HyOMe‐W5:siF3 nanoparticles, FADD knockdown was maximal (60%) for 40 nM siF3. FADD silencing did not increase with increasing siRNA concentration, probably due to the dose‐dependent increase in cytotoxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,449,BE-ST@siBACE1 / BE-ST@siRNA,siRNA,BACE1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,A,Results > Brain-targeted delivery of siBACE1 by BE-ST for AD treatment; paragraph 18,9961,Berberine-inspired ionizable lipid for self-structure stabilization and brain targeting delivery of nucleic acid therapeutics.,40064874,PMC11893799,10.1038/s41467-025-57488-0,https://pubmed.ncbi.nlm.nih.gov/40064874/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Blood biochemistry and histological analyses two weeks post-injection showed no significant differences between PBS and BE(-ST)@siRNA groups (Supplementary Figs. 21, 22 and Tables 9, 10).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,450,PEI/PHD2 siRNA nanocomplexes,siRNA,PHD2,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results > Biological effects of PEI/PHD2 SiRNA complexes on HUVECs; paragraph 36,12938,Optimized delivery of RNA silencing prolyl hydroxylase domain 2 for enhanced angiogenesis and osteogenesis using bioactive glass scaffolds.,41266661,PMC12634668,10.1038/s41598-025-24808-9,https://pubmed.ncbi.nlm.nih.gov/41266661/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"After 24 h of exposure to the complexes at a concentration of 20 µM, the viability of HUVECs remained > 90% across all the tested N: P ratios (3:1, 6:1, and 8:1), indicating the biocompatibility and nontoxicity of the nanocomplexes (Fig. 2A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,451,PLGA-CpG@ID8-M nanovaccine,CpG oligodeoxynucleotide,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,"Results and Discussion > Synthesis, Characterization, and Safety Assessment of PLGA-CpG@ID8-M Nanovaccine; paragraph 9",13359,CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages.,39985265,PMC12005807,10.1002/advs.202412881,https://pubmed.ncbi.nlm.nih.gov/39985265/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Neither PLGA‐CpG@ID8‐M nor free CpG significantly affected cell viability at concentrations of 0–2 µm, while obvious cytotoxicity was observed at concentrations exceeding 4 µm (Figure 1F).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,452,siRNA SORT LNPs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,Results > SORT LNPs enable robust silencing of tissue-enriched endogenous gene targets and are well tolerated in vivo.; paragraph 12,2577,"Expanding RNAi to Kidneys, Lungs, and Spleen via Selective ORgan Targeting (SORT) siRNA Lipid Nanoparticles.",38973655,PMC11823468manuscript-id: NIHMS2006301,10.1002/adma.202313791,https://pubmed.ncbi.nlm.nih.gov/38973655/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There were no significant differences in biomarkers observed between siRNA SORT LNPs and PBS groups.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,453,Ube3a-AS ASO,ASO,Ube3a-AS,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Analysis of potential toxicities of ASO exposure in dams; paragraph 15,2614,Prenatal delivery of a therapeutic antisense oligonucleotide achieves broad biodistribution in the brain and ameliorates Angelman syndrome phenotype in mice.,38327047,PMC11163203,10.1016/j.ymthe.2024.02.004,https://pubmed.ncbi.nlm.nih.gov/38327047/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We observed an elevation in aspartate aminotransferase (AST) in the dams of IC-injected pups, and a trend for AST elevation in dams of IA-injected pups compared with dams of PBS-injected controls",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,454,CD44 siRNA nanoplexes,siRNA,CD44,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,3. Results > 3.4. siRNA Delivery Cytotoxicity of Complexes Developed in This Study; paragraph 24,10973,Development of Focused Ultrasound-Assisted Nanoplexes for RNA Delivery.,38998694,PMC11243722,10.3390/nano14131089,https://pubmed.ncbi.nlm.nih.gov/38998694/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No statistical significance was detected with any formulation in any of the cell lines. Cell viability was above 60 percent in all formulations with both cell lines.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,455,Phe-NPs/ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,"Results > In vitro characterization of Phe-NPs/ASO: Cellular uptake, endosomal escape, cell viability, and cytotoxicity; paragraph 11",12161,l-Type amino acid transporter 1-targeting nanoparticles for antisense oligonucleotide delivery to the CNS.,39411247,PMC11474373,10.1016/j.omtn.2024.102340,https://pubmed.ncbi.nlm.nih.gov/39411247/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There were no significant effects on cell viability or cytotoxicity following exposure to NT-NPs/ASO or Phe-NPs/ASO at any of the tested concentrations,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,456,DOTAP/siSmad4@EM,siRNA,Smad4,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,A,Results and discussion > Safety profiles; paragraph 46,12475,Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment.,39258001,PMC11385781,10.1016/j.ajps.2024.100929,https://pubmed.ncbi.nlm.nih.gov/39258001/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"DOTAP/siRNA@EM having highest siRNA concentration (200 nM) displayed the lowest cytotoxicity (cell viability, ∼80 %) following 48 h-treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,457,TPNs-siRNA,siRNA,MMP-2/MMP-9,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,Results and discussion > Safety assessment of TPNs-siRNA; paragraph 67,12485,Tea polyphenol nanoparticles enable targeted siRNA delivery and multi-bioactive therapy for abdominal aortic aneurysms.,39118143,PMC11308685,10.1186/s12951-024-02756-2,https://pubmed.ncbi.nlm.nih.gov/39118143/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"At concentrations ranging from 10 to 100 µg/mL, the cell viability exceeded 90% (Fig. 2A, B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,459,AA-T3A-C12/siHSP47 LNP,siRNA,HSP47,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety evaluation; paragraph 19,4035,Ligand-tethered lipid nanoparticles for targeted RNA delivery to treat liver fibrosis.,36650129,PMC9845313,10.1038/s41467-022-35637-z,https://pubmed.ncbi.nlm.nih.gov/36650129/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"AA-T3A-C12/siHSP47 LNP treatment slightly decreased ALT, AST, and TBIL levels in fibrotic mice, but these decreases were not significant.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,460,r/si-ORF7 flexible nano-liposomes,siRNA,ORF7,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,B,Results > Preparation and characterization of flexible nano-liposomes; paragraph 18,12511,A novel recombinant ORF7-siRNA delivered by flexible nano-liposomes inhibits varicella zoster virus infection.,37700336,PMC10496174,10.1186/s13578-023-01108-1,https://pubmed.ncbi.nlm.nih.gov/37700336/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,the r/si-ORF7 displayed negligible cytotoxicity to ARPE-19 cells till 100 nM that was 10 folds higher than its working concentration (10 nM) used in antiviral experiments,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,461,MPLN siRNA nanoparticles,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results > Cytotoxicity; paragraph 19,12533,Lymphocyte Membrane- and 12p1-Dual-Functionalized Nanoparticles for Free HIV-1 Trapping and Precise siRNA Delivery into HIV-1-Infected Cells.,36755201,PMC10074117,10.1002/advs.202300282,https://pubmed.ncbi.nlm.nih.gov/36755201/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,there was no significant change found in cell viability for all three cell lines treated with MLN or MPLN compared with control,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,462,ZNF416 siRNA-loaded liposomes,siRNA,ZNF416,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,Results > Administration of ZNF416 siRNA-loaded liposomes attenuates pulmonary fibrosis in experimental mouse models; paragraph 41,12545,Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.,36371191,PMC9652794,10.1186/s12967-022-03740-w,https://pubmed.ncbi.nlm.nih.gov/36371191/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We also found no significant differences in these markers of the liver, kidney, and heart function and body weight in comparison with controls",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,463,CS-OA coated PLGA siRNA nanoparticles,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,3. Results and Discussion > 3.4. Cytotoxicity Test on Human CD14+ Monocytes from Peripheral Blood; paragraph 23,4114,Chitosan Oleate Coated PLGA Nanoparticles as siRNA Drug Delivery System.,34684009,PMC8539707,10.3390/pharmaceutics13101716,https://pubmed.ncbi.nlm.nih.gov/34684009/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The results demonstrated that the presence of CS-NPs, including at the highest concentration of CS-OA (100 μg/mL), did not affect cell viability.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,465,siSTAT3/DoCh LNP,siRNA,STAT3,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,3. Results and Discussion; paragraph 27,4197,Silencing of STAT3 via Peptidomimetic LNP-Mediated Systemic Delivery of RNAi Downregulates PD-L1 and Inhibits Melanoma Growth.,32059541,PMC7072202,10.3390/biom10020285,https://pubmed.ncbi.nlm.nih.gov/32059541/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,measurement of serum ALT/AST level showed that nontreated and siSTAT3/DoCh-treated group had normal level of the liver enzymes,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,469,fully chemically modified hsiRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,B,RESULTS > Full chemical stabilization enables productive silencing in vivo.; paragraph 35,12636,Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo.,29432571,PMC5861422,10.1093/nar/gky037,https://pubmed.ncbi.nlm.nih.gov/29432571/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 29432571; weak/generic or abstract-limited support for general safety/systemic safety/tolerability.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,470,Br-ApoE(K->A)-PMO and related P-PMO conjugates,PMO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Results > PMO conjugation and cellular assays as measures of cell uptake ability; paragraph 25,12658,Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy.,28118087,PMC5467147,10.1089/nat.2016.0652,https://pubmed.ncbi.nlm.nih.gov/28118087/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Compared with untreated cells, no significant reductions in cell viability were seen for any conjugate",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,474,ISIS 405879 2'-MOE ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematological,thrombocytopenia,B,PubMed abstract,2090,Complement C3d/C4d Deposition on Platelets Correlates with 2'-O-Methoxyethyl Antisense Oligonucleotide-Induced Thrombocytopenia in Monkeys.,37093125,,10.1089/nat.2022.0042,https://pubmed.ncbi.nlm.nih.gov/37093125/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hematological/thrombocytopenia in ISIS 405879 2'-MOE ASO; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,475,unspecified ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety evaluation; paragraph 25,1055,Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.,42095135,PMC13140060,10.1016/j.omtn.2026.102930,https://pubmed.ncbi.nlm.nih.gov/42095135/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,WRN-108 was well tolerated in both species up to the highest doses tested.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,476,unspecified ASO (PMID:41981306),ASO,,,,,,,,,,,,unspecified,unspecified,general safety,systemic safety/tolerability,A,Results > Safety characterization and IND-enabling studies; paragraph 15,1058,Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.,41981306,PMC13099374,10.1038/s41591-026-04314-9,https://pubmed.ncbi.nlm.nih.gov/41981306/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,We therefore considered the serious adverse events encountered in our two patients to be attributable to dosing of the study drug.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,477,"TLK2 ASO (recovered B2 from PMID:41878536, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results; paragraph 24,1062,Targeting TLK2 with antisense oligonucleotides as a new strategy in acute myeloid leukemia.,41878536,PMC13006219,10.3389/fonc.2026.1659341,https://pubmed.ncbi.nlm.nih.gov/41878536/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The toxicity study showed that ALT levels in the TLK2 ASO group were slightly elevated, but the combination treatment reduced ALT levels.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,478,unspecified ASO (PMID:42033225),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > F-ASO gapmers reduce disease-associated repeat RNA foci in patient-derived NSCs; paragraph 32,1185,Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.,42033225,PMC13109722,10.1093/nar/gkag343,https://pubmed.ncbi.nlm.nih.gov/42033225/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No significant reduction in cell viability was observed for ASO3 or ASO4 at 50 nM total ASO concentration,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,479,siRNA-Lipid,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > In Vivo Therapeutic Efficacy Evaluation in Various Mouse Models; paragraph 39,1193,DNA Repair Enzyme Regulation Strategy for Enhanced Pancreatic Neuroendocrine Tumor Therapy via Targeting siRNA-Lipid Nanoparticles.,41919978,PMC13085844,10.1021/acsnano.5c21452,https://pubmed.ncbi.nlm.nih.gov/41919978/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In contrast, the LOTR-treated group showed hematological parameters comparable to those of the PBS control, suggesting reduced systemic toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,480,CO2,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,Materials and methods > Assessment of oligonucleotide toxicity (LD50) using the MTT assay; paragraph 13,1210,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1.,41704705,PMC12907196,10.3389/fmed.2026.1719202,https://pubmed.ncbi.nlm.nih.gov/41704705/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The characteristic features included low toxicity (maintaining >92% viable cells after 48 h of culture),2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,481,"siRNA2 (recovered B2 from PMID:42005705, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Cytotoxicity of mPEG-Azo-PEI; paragraph 50,1368,Preparation and Antitumor Activity of METTL3 SiRNA Nanoparticles Carried by Hypoxia Sensitive Polymer (mPEG-Azo-PEI).,42005705,PMC13091633,10.2147/IJN.S588018,https://pubmed.ncbi.nlm.nih.gov/42005705/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,These results demonstrate that mPEG-Azo-PEI@siRNA2 exhibits minimal non-specific toxicity toward normal cells.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,482,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > Synergistic Effect of Ferroptosis Induction via GPX4 Inhibition and PDT; paragraph 15,1773,Photosensitizing Lipid Nanoparticles for Ferroptosis-Enhanced Photodynamic Cancer Therapy via GPX4 Silencing.,41220296,PMC12908211,10.1002/adhm.202503748,https://pubmed.ncbi.nlm.nih.gov/41220296/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No significant changes in body weight were observed across treatment groups. Blood chemistry and histopathological analyses also confirmed the excellent biocompatibility of PLNPs, with no observable adverse effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,483,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,RESULTS > siPAI-1 does not elicit overt toxicity in vivo.; paragraph 22,2412,Silencing of PAI-1 using siRNA-lipid nanoparticles reduces thrombosis and prolongs life span in murine models.,41587091,PMC12994142manuscript-id: NIHMS2150465,10.1182/blood.2025029834,https://pubmed.ncbi.nlm.nih.gov/41587091/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To assess acute toxicity, we analyzed the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) 5 hours post-injection in young adult mice. No significant changes were observed between siPAI-1 and PBS injected mice",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,485,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > The siLin28b Plus BMN673 Combination Inhibits the Deterioration of Vascular Permeability; paragraph 44,3294,PARPi Combining Nanoparticle LIN28B siRNA for the Management of Malignant Ascites.,41572432,PMC13042977,10.1002/advs.202510547,https://pubmed.ncbi.nlm.nih.gov/41572432/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Subsequently, we evaluated the biosafety profiles of siLin28b+BMN673 in tumor‐free mice. Major organs including the heart, liver, spleen, lung, and kidney were collected and subjected to H&E staining. The histopathological analysis revealed no significant differences between the groups treated with siLin28b+BMN673 or vehicle, with nuclear and cellular morphologies remaining unchanged post‐treatment (Figure S10a). Consistently, a comprehensive blood analysis assessing six key toxicity parameters demonstrated comparable levels between the siLin28b+BMN673 and vehicle groups (Figure S10b), indicating no discernible impact on hepatic or renal function.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,492,"eteplirsen (recovered B2 from PMID:41961051, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Treatment continuation; paragraph 33,5375,"Advancements from the EVOLVE study for assessing real-world experience with eteplirsen, golodirsen and casimersen for the treatment of DMD.",41961051,PMC13154584,10.57264/cer-2025-0108,https://pubmed.ncbi.nlm.nih.gov/41961051/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"All PMOs demonstrated favorable safety profiles, with no treatment-emergent serious adverse events related to treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,499,tofersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,Results > Safety; paragraph 35,6390,Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.,41661214,PMC12723595,10.1001/jamaneurol.2025.4946,https://pubmed.ncbi.nlm.nih.gov/41661214/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No new safety concerns were identified with long-term exposure to tofersen.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,500,unspecified ASO (PMID:41630990),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Safety evaluation through serum biochemistry; paragraph 22,6475,Improving angiogenesis ameliorates the efficacy of ASO-based exon skipping for the treatment of Duchenne muscular dystrophy.,41630990,PMC12860987,10.1016/j.omtn.2026.102834,https://pubmed.ncbi.nlm.nih.gov/41630990/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Finally, to evaluate potential treatment-related toxicity, serum biochemical markers were assessed in mdx mice across all groups (i.e., AAV-mLVRF alone, ASO alone, or the combined mLVRF+ASO). No significant changes were detected in serum urea, albumin, or creatinine",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,509,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > Cytotoxicity Assessment of Dendrimers; paragraph 43,7065,Hydrolytically Stable Cationic Bis-MPA Dendrimers as Efficient Transfectants for Glioblastoma Cells and Primary Astrocytes.,41334811,PMC12801319,10.1021/acs.biomac.5c01202,https://pubmed.ncbi.nlm.nih.gov/41334811/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"despite its efficacy, g3-cys displayed a narrow therapeutic window with pronounced cytotoxicity above 1 μm. in vivo studies further confirmed dose-dependent systemic toxicity, likely associated with enhanced blood coagulation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,510,"unspecified CpG oligodeoxynucleotide (v1 extraction artefact, pending source re-verification)",CpG oligodeoxynucleotide,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > In Vitro Photo‐Controlled Activation and Cytotoxicity of PURH; paragraph 13,7129,Spatiotemporally Controlled Tumor Photodynamic/Immunotherapy Therapy Based on Upconversion Hybrid Nanosystem.,41270206,PMC12866702,10.1002/advs.202515052,https://pubmed.ncbi.nlm.nih.gov/41270206/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"These results indicated that PURH not only significantly inhibited tumor growth, but also did not induce liver toxicity, demonstrating that PURH has good biological safety.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,511,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,A,Results > PDL E inhibits viability of MDA-MB-231 DOX RT cells in 2D and 3D cultures; paragraph 36,7336,Genetically bio-engineered PD-L1 targeted exosomes for immunotherapy of resistant triple negative breast cancer.,40762902,PMC12893402manuscript-id: NIHMS2134215,10.1007/s13346-025-01920-x,https://pubmed.ncbi.nlm.nih.gov/40762902/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To evaluate the off-target toxicity of PDL E, cytotoxicity assays were conducted using MCF-10 A cells. The results demonstrated that PDL E exhibited no detectable toxicity in these non-cancerous cells, supporting the safety profile of these exosomes for therapeutic applications (Supplementary Fig. 3).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,512,"elsunersen (recovered B2 from PMID:40263630, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Methods > Patient eligibility; paragraph 16,1013,Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy.,40263630,PMC12283366,10.1038/s41591-025-03656-0,https://pubmed.ncbi.nlm.nih.gov/40263630/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Vital signs and blood tests did not reveal any persistent abnormalities that could be directly attributed to the administration of elsunersen within the observed timeframe.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,513,"ASO 8–3 (recovered B2 from PMID:40098305, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > ASO 8–3419 Enhances the Therapeutic Effect of Cisplatin in Xenografted HCT116 Tumors in Nude Mice; paragraph 26,1020,AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds.,40098305,PMC12044654,10.1111/cas.70024,https://pubmed.ncbi.nlm.nih.gov/40098305/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"aso 8–3419 administration resulted in a moderate increase in alt levels, but no increase in ast levels (figure 8a), indicating that the toxicity of systemically administered aso 8–3419 is mild and tolerable.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,514,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Subcutaneous administration allows for optimal distribution and is not toxic to mice; paragraph 14,1233,Restoring chloride efflux in cystic fibrosis with TMEM16a antisense oligonucleotides.,40926414,PMC12703169,10.1016/j.ymthe.2025.08.045,https://pubmed.ncbi.nlm.nih.gov/40926414/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,by measuring lactate dehydrogenase (LDH) levels and identified no differences up to 200 mM (Figure 3B).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,516,single-patient,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract > Methods; paragraph 2,1254,"Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series.",40414239,PMC12407188manuscript-id: NIHMS2086788embargo-date: 2026/06/07,10.1016/S0140-6736(25)00513-6,https://pubmed.ncbi.nlm.nih.gov/40414239/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The most common adverse events were back pain (six [50%]), headache (four [33%]), nausea (three [25%]), and post-lumbar puncture headache (three [25%]).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,517,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,RESULTS > Prenatal IA ASO administration enhances therapeutic efficacy in SMAΔ7 mice; paragraph 10,1256,Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.,40367190,PMC12423764manuscript-id: NIHMS2101949,10.1126/scitranslmed.adv4656,https://pubmed.ncbi.nlm.nih.gov/40367190/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,ASOs delivered by IA injection distributed to the spinal cord at therapeutic concentrations and to multiple peripheral tissues without evidence of significant toxicity to the fetus or mother.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,518,AZD8701,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety > AZD8701 monotherapy; paragraph 39,1270,"AZD8701, an Antisense Oligonucleotide Targeting FOXP3 mRNA, as Monotherapy and in Combination with Durvalumab: A Phase I Trial in Patients with Advanced Solid Tumors.",39937271,PMC11995004,10.1158/1078-0432.CCR-24-1818,https://pubmed.ncbi.nlm.nih.gov/39937271/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,One dose-limiting toxicity (increased alanine aminotransferase) occurred with AZD8701 960 mg.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,520,"Chol-HDO[PMO] (recovered B2 from PMID:41429785, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Safety evaluation of Chol-HDO[PMO]; paragraph 27,1783,"Morpholino-RNA duplex exhibits robust, sustained, and safe steric-block antisense activity by intracerebroventricular and intrathecal injection.",41429785,PMC12722745,10.1038/s41467-025-66765-x,https://pubmed.ncbi.nlm.nih.gov/41429785/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Chol-HDO[PMO] was well tolerated even at the highest dose (40 nmol), whereas ssMOEs exhibited lethal toxicity in a dose-dependent manner (Fig. 4b).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,522,"iExoKrasG12D (recovered B2 from PMID:41027940, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > GMP grade exosomes for siRNA delivery showed no toxicity in preclinical studies; paragraph 6,1803,Engineered exosomes with Kras(G12D) specific siRNA in pancreatic cancer: a phase I study with immunological correlates.,41027940,PMC12485160,10.1038/s41467-025-63718-2,https://pubmed.ncbi.nlm.nih.gov/41027940/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No related adverse events were noted for any patients at the dose levels tested in the 3 + 3 Phase Ia trial,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,527,"STP705 (recovered B2 from PMID:39692702, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract > Methods; paragraph 3,2535,A Novel Injectable Polypeptide Nanoparticle Encapsulated siRNA Targeting TGF-β1 and COX-2 for Localized Fat Reduction II: Phase I Clinical Trial.,39692702,PMC11845920,10.1111/jocd.16722,https://pubmed.ncbi.nlm.nih.gov/39692702/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"STP705 demonstrated a favorable safety profile with no clinically significant changes in lab values, vital signs, or ECGs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,528,"PDA@Mn-siSur-c-NPs (recovered B2 from PMID:41599118, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,3. Results and Discussion > 3.12. Safety Evaluation; paragraph 56,3399,Construction and Characterization of PDA@MnO(2)-Cored Multifunctional Targeting Nanoparticles Loaded with Survivin siRNA for Breast Tumor Therapy.,41599118,PMC12844724,10.3390/pharmaceutics18010010,https://pubmed.ncbi.nlm.nih.gov/41599118/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"As for the measurement of biochemical indicators, compared to the model group, there were no significant differences in AST, ALT, BUN, or CRE activity among the mice in each group (Table 4).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,529,"D-siRNA (recovered B2 from PMID:41473322, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,"RESULTS > D-siRNA supports safe, potent and durable activity in the CNS; paragraph 24",3402,Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.,41473322,PMC12746015,10.64898/2025.12.16.694641,https://pubmed.ncbi.nlm.nih.gov/41473322/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Analysis of toxicity indicators iba1 and gfap in the thalamus and hippocampus—regions closest to the injection site with the highest siRNA accumulation and activity (8)—showed no observed changes, supporting the safety of D-siRNA (Figure 2B, right panel).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,530,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Muscle-optimal siRNA scaffold achieves systemic muscle effects and has a favorable safety profile; Figure 6. caption,3407,Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.,41432033,PMC12723224,10.1093/nar/gkaf1374,https://pubmed.ncbi.nlm.nih.gov/41432033/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Compared to the controls, the 40 mg/kg and 40 mg/kg/2wks treatments did not increase liver (ALT) or kidney (BUN) damage markers",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,531,elebsiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety profiles of KC13-M2G2 in SD rats and cynomolgus monkeys; paragraph 19,3426,An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection.,41326382,PMC12780110,10.1038/s41467-025-66876-5,https://pubmed.ncbi.nlm.nih.gov/41326382/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The animals can well tolerate the challenge of repeat doses of KC13-M2G2 even at the highest tested dose of 200 mg/kg,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,533,"KFFK (FFK)2-conjugated PNA (recovered B2 from PMID:41096791, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,A,2. Results > 2.2. Cytotoxicity of CPP–PNA Conjugates in Mammalian Cells; paragraph 7,3472,Targeting carA Using Optimized Antisense Peptide Nucleic Acid-Cell-Penetrating Peptide Conjugates in Acinetobacter baumannii: A Novel Antibacterial Approach.,41096791,PMC12525168,10.3390/ijms26199526,https://pubmed.ncbi.nlm.nih.gov/41096791/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"At 12.5 µM, the treatment group exhibited cytotoxic effects comparable to those of the positive control (10% DMSO), showing statistically significant toxicity in HEp-2 and A549 cells",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,538,unspecified ASO (PMID:40736236),ASO,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,B,OBSERVATION; Fig 1 caption,3573,An antisense peptide-conjugated peptide nucleic acid (PPNA) for peptidoglycan recycling inhibition reduces AmpC hyperproduction and β-lactam resistance in Pseudomonas aeruginosa.,40736236,PMC12403870,10.1128/spectrum.02622-24,https://pubmed.ncbi.nlm.nih.gov/40736236/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"after NagZ-PPNA treatment at 2 and 4 µM, values of this parameter were ca. 6% and 10% respectively",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,539,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,C,Results and Discussion > Biocompatibility of Cleavable Dendrimers; paragraph 51,3596,Cleavable Cationic Carbosilane Dendrimers with pH-Tunable Charge as siRNA Carriers.,40679089,PMC12344721,10.1021/acs.biomac.5c00344,https://pubmed.ncbi.nlm.nih.gov/40679089/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Dendrimers 2 and 3 were biocompatible in PBMCs up to 1 and 0.5 μM, respectively, and slightly higher concentrations in THP-1 (1 μM).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,540,"L2-siRNA (recovered B2 from PMID:40598893, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > L2-siRNA does not induce hallmarks of toxicity; paragraph 54,3619,Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid-siRNA conjugate administered into cerebrospinal fluid.,40598893,PMC12214009,10.1093/nar/gkaf600,https://pubmed.ncbi.nlm.nih.gov/40598893/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We provide a detailed examination of regional bulk tissue gene silencing in mice, highlighting potent knockdown 5 months after a single injection without detectable toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,543,"HSA@ICG/siRNA NPs (recovered B2 from PMID:40259913, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Anti-Tumor Efficacy and Safety Evaluation in Vivo; paragraph 63,3710,NIR-Triggered siRNA Release and Lysosomal Escape for Synergistic Photothermal Tumor Therapy.,40259913,PMC12010081,10.2147/IJN.S511655,https://pubmed.ncbi.nlm.nih.gov/40259913/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40259913; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,544,unspecified siRNA (PMID:40143003),siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,A,2. Materials and Methods > 2.8. Acute Toxicity (LDH Release); paragraph 25,3725,Analysis of Polymer/siRNA Nanoparticle Efficacy and Biocompatibility in 3D Air-Liquid Interface Culture Compared to 2D Cell Culture.,40143003,PMC11946471,10.3390/pharmaceutics17030339,https://pubmed.ncbi.nlm.nih.gov/40143003/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Tyrosine-modified nanoparticles, in particular P10Y-based polyplexes or lipopolyplexes, showed the highest biocompatibility.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,545,unspecified siRNA (PMID:39906612),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Conclusion; paragraph 41,3765,Nanomolecular silencing of TSC22D4 mRNA via a DNAsome-siRNA for enhancing insulin sensitization in hepatocytes.,39906612,PMC11790197,10.22038/ijbms.2024.81998.17744,https://pubmed.ncbi.nlm.nih.gov/39906612/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,the cell survival in the samples treated with nanocarrier/siRNA complex at 10 and 20 nanomolar concentrations was 99.3% and 99.2%,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,546,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,renal,renal safety,A,2. Materials and Methods > 2.8. Toxicity Pathways Evaluation; paragraph 22,3771,A Novel Approach for In Vitro Testing and Hazard Evaluation of Nanoformulated RyR2-Targeting siRNA Drugs Using Human PBMCs.,39860035,PMC11766699,10.3390/life15010095,https://pubmed.ncbi.nlm.nih.gov/39860035/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No changes in IL-8, IL-6, and IFN-γ releases were observed after CaP-siRNA or, CaP-scramble (Figure 3B–D).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,548,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > Reduced 5’ end- and -2’- fluoro modification design; paragraph 37,3801,"Design, Screening and Development of Asymmetric siRNAs Targeting the MYC Oncogene in Triple-Negative Breast Cancer.",39632755,PMC11704396,10.4062/biomolther.2024.071,https://pubmed.ncbi.nlm.nih.gov/39632755/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,neither the single 400 µg dose nor the 300 µg repeated doses of asiRNA-VP-DCA induced any signs of toxicity or mortality in either treatment group,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,551,Silica,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results and Discussion > Specific Gene Silencing Studies; paragraph 21,7559,"Modular Design of Mesoporous Silica Nanoparticles Enables Bioimaging, Dual Chemotherapy, and Combinatorial Gene Silencing in Triple-Negative Breast Cancer.",41392621,PMC12754758manuscript-id: NIHMS2132376,10.1021/acsami.5c15253,https://pubmed.ncbi.nlm.nih.gov/41392621/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In contrast, no measurable IRF activation was detected for complexes containing RNA fibers or DS RNA with either MSN-PEI formulation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,556,"siPCSK9 (recovered B2 from PMID:41290746, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > NP containing PCSK9 siRNA and STING agonists enable safe and effective cancer immunotherapy; paragraph 17,7717,Silencing PCSK9 reshapes the spatiotemporal activation of STING for safe and effective cancer immunotherapy.,41290746,PMC12749358,10.1038/s41467-025-66630-x,https://pubmed.ncbi.nlm.nih.gov/41290746/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"exhibited excellent safety profiles, without body weight changes at 24 h and 48 h post-administration",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,560,unspecified siRNA (PMID:41226635),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,2. Results > 2.4. Evaluation of the Cytotoxic Effects of Ternary Polyplexes; paragraph 22,7835,Anti-Angiogenic RNAi-Based Treatment of Endometriosis in a Rat Model Using CXCR4-Targeted Peptide Nanoparticles.,41226635,PMC12607363,10.3390/ijms262110582,https://pubmed.ncbi.nlm.nih.gov/41226635/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The results shown in Figure 3 indicate that no significant differences in cytotoxicity were observed among the coated polyplexes across all tested charge ratios in MDA-MB-231 cells.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,565,"PUMCH-E13 (recovered B2 from PMID:40970667, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,article body; paragraph 6,8330,Exon Skipping Therapy Restores Ciliary Function in USH2A-Related Retinal Degeneration.,40970667,PMC12453064,10.1167/iovs.66.12.46,https://pubmed.ncbi.nlm.nih.gov/40970667/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No significant adverse effects were observed through apoptosis assays or ERG.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,566,siPD-L1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Inhalation of mscFv/siPD-L1@LNP drives TME reconfiguration in orthotopic lung tumors; paragraph 15,8508,Modulating tumor collagen fiber alignment for enhanced lung cancer immunotherapy via inhaled RNA.,40885724,PMC12398490,10.1038/s41467-025-63415-0,https://pubmed.ncbi.nlm.nih.gov/40885724/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"H&E staining of major organs, including the heart, liver, spleen, and kidneys, showed no lesions, histopathological injuries, or abnormalities caused by the inhalation of mscFv/siPD-L1@LNP (Supplementary Fig. 24b).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,568,unspecified siRNA (PMID:40848064),siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,B,Materials and methods > Cell viability assay; paragraph 25,8603,"Heat up, silence on: IDO1 gene silencing in THP-1-derived dendritic cells triggered by magnetic hyperthermia.",40848064,PMC12374930,10.1007/s00262-025-04148-3,https://pubmed.ncbi.nlm.nih.gov/40848064/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40848064; weak/generic or abstract-limited support for general safety/cell viability/cytotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,571,inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 11,9021,Treatment With Inclisiran During Peritoneal Dialysis.,40645721,PMC12441398,10.1016/j.jaccas.2025.103897,https://pubmed.ncbi.nlm.nih.gov/40645721/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40645721; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,572,unspecified PMO (PMID:40608957),PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Discussion; paragraph 48,9102,Exon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy.,40608957,PMC12677909,10.1093/brain/awaf249,https://pubmed.ncbi.nlm.nih.gov/40608957/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"These data support that systemically administered PPMO6 resulted in a better targeting of DNM2 level in the muscle than in the liver, with no signs of toxicity in the liver.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,574,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,9180,Intravenous Administration of sRNA Nanoparticles for Treatment of Osteoporosis in Mice.,40574101,PMC12196915,10.3390/pharmaceutics17060789,https://pubmed.ncbi.nlm.nih.gov/40574101/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Comprehensive safety evaluation (Figure 6) demonstrated that LNP-sRNA treatment did not adversely affect physiological parameters such as food intake or body weight over a 14-day treatment period.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,576,"si-Cx43 (recovered B2 from PMID:40528841, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Discussion; paragraph 47,9274,Thermosensitive hydrogel composite with si-Cx43 nanoparticles and anti-VEGF agent for synergistic treatment of diabetic retinopathy.,40528841,PMC12173670,10.1016/j.mtbio.2025.101917,https://pubmed.ncbi.nlm.nih.gov/40528841/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In the CCK-8 assay, compared to the control group, single si-Cx43-NPs, single Avastin, non-loaded hydrogel, Avastin-hydrogel, and si-Cx43-NPs@Avastin-hydrogel did not significantly reduce cell viability, indicating low cytotoxicity, whereas cisplatin significantly suppressed cell viability (Fig. 3B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,578,"DG9-PMO (recovered B2 from PMID:40368879, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > DG9-PMO facilitates enhanced cellular uptake and efficacious nuclear localization; paragraph 9,9560,DG9 boosts PMO nuclear uptake and exon skipping to restore dystrophic muscle and cardiac function.,40368879,PMC12078682,10.1038/s41467-025-59494-8,https://pubmed.ncbi.nlm.nih.gov/40368879/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Here, we found no significant difference between any treatment groups suggesting no apparent toxic effects of DG9-PMO on the kidney.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,581,unspecified siRNA (PMID:40297405),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > In vitro Antitumor Effect of E-cLip-DTX / Si; paragraph 46,9662,ROS-Responsive Biomimetic Nanocomplexes of Liposomes and Macrophage-Derived Exosomes for Combination Breast Cancer Therapy.,40297405,PMC12036690,10.2147/IJN.S514375,https://pubmed.ncbi.nlm.nih.gov/40297405/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 40297405; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,583,"D-siRNA-Plk1 (recovered B2 from PMID:40236812, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and discussion > In vivo anti-tumor activity of DS-ARGN; paragraph 25,9750,Bundling gold nanorods with RCA-produced DNA tape into an intelligently reconfigurable nanocluster bomb for multimodal precision cancer therapy.,40236812,PMC11999372,10.1016/j.mtbio.2025.101718,https://pubmed.ncbi.nlm.nih.gov/40236812/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40236812; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,586,unspecified siRNA (PMID:40207309),siRNA,,,,,,,,,,,,unspecified,unspecified,general toxicity,toxicity,B,Abstract > Methods; paragraph 2,9792,Si-ITGA6-Loaded Liposomes Inhibit Capsule Fibrosis via the FAK/PI3K/Akt Signaling Pathway in Adhesive Capsulitis of Shoulder.,40207309,PMC11980806,10.2147/IJN.S501561,https://pubmed.ncbi.nlm.nih.gov/40207309/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The results indicated that there was no significant decrease of NIH3T3s viability when the si-ITGA6-loaded liposomes reached a concentration of 200 nM,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,587,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,A,Results > Three-month rat toxicology study; paragraph 38,9966,Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.,40060931,PMC11889396,10.1016/j.omtn.2025.102479,https://pubmed.ncbi.nlm.nih.gov/40060931/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"VCA-894A administration on days 1, 29, 57, and 85 was well tolerated at all dose levels and there were no unscheduled deaths during the course of the study.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,588,"AS-T9/U4_MH (recovered B2 from PMID:39946362, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and discussion > Effect of Dox-loaded AS-T9/U4_MH on cell proliferation; paragraph 31,10132,"Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and T9/U4 ASO.",39946362,PMC11825018,10.1371/journal.pone.0317559,https://pubmed.ncbi.nlm.nih.gov/39946362/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 39946362; pmc_full_text evidence was direct but less than full primary-detail confidence for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,589,unspecified CpG (PMID:39838063),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Safety aspects of the lead candidate AON; paragraph 43,10245,Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.,39838063,PMC11751084,10.1038/s43856-024-00712-7,https://pubmed.ncbi.nlm.nih.gov/39838063/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 39838063; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,598,unspecified ASO (PMID:39460376),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Pre-saturation with calcium reduces acute neurotoxicity; paragraph 25,1282,Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.,39460376,PMC11638874,10.1016/j.ymthe.2024.10.024,https://pubmed.ncbi.nlm.nih.gov/39460376/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Reducing the PS content of gapmer ASOs, which contain a stretch of PS-DNA, improves their toxicity profile, but in some cases also reduces efficacy or duration of effect.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,600,"ION-827359 (recovered B2 from PMID:39286058, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Methods > End-points > Safety; paragraph 13,1562,"Randomised, phase 1/2a trial of ION-827359, an antisense oligonucleotide inhibitor of ENaC.",39286058,PMC11403593,10.1183/23120541.00986-2023,https://pubmed.ncbi.nlm.nih.gov/39286058/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"ION-827359 was well tolerated with an acceptable safety profile. There were no clinically relevant changes in laboratory values, ECG or vital signs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,601,Site-blocking,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,DISCUSSION > Risk of adverse effects; paragraph 53,2556,Site-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression.,39379106,PMC11571808,10.1261/rna.080220.124,https://pubmed.ncbi.nlm.nih.gov/39379106/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Conversely, mice administered sbASO.miR-483 exhibited severe adverse phenotypes, including ataxia and orofacial dyskinesia, resulting in euthanasia before the full 5-day postimplantation period.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,602,siRNA-mediated,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > siRNA-LNPs displayed a low risk of CARPA and other toxicities; paragraph 9,2588,siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.,38779336,PMC11109470,10.1016/j.omtm.2024.101258,https://pubmed.ncbi.nlm.nih.gov/38779336/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Clinical signs of CARPA were not observed, and occasional mild and transient hepatotoxicity was present in siPLG-treated animals at 5 h post-infusion, which returned to baseline by 7 days.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,603,unspecified ASO (PMID:38276948),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,2618,An antisense oligonucleotide efficiently suppresses splicing of an alternative exon in vascular smooth muscle in vivo.,38276948,PMC11221813,10.1152/ajpheart.00745.2023,https://pubmed.ncbi.nlm.nih.gov/38276948/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 38276948; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,604,"NANP-siRhoA (recovered B2 from PMID:40308740, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,RESULTS AND DISCUSSION; paragraph 20,3813,The Reduction of Traumatic Spinal Cord Secondary Injury by Anti-RhoA siRNA Functionalized Nucleic Acid Nanoparticles (NANPs).,40308740,PMC12043328manuscript-id: NIHMS2068822,10.59566/isrnn.2024.0101079,https://pubmed.ncbi.nlm.nih.gov/40308740/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Cell viability assays in THP1 Dual cells revealed an approximately 50% reduction in viability when NANP-siRhoAs were complexed with the L2K carrier (Fig. 8A).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,605,unspecified siRNA (PMID:39296267),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,3848,Lipopolymer/siRNA Nanoparticles Targeting the Signal Transducer and Activator of Transcription 5A Disrupts Proliferation of Acute Lymphoblastic Leukemia.,39296267,PMC11406681,10.1021/acsptsci.4c00336,https://pubmed.ncbi.nlm.nih.gov/39296267/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The lipopolymers did not induce the secretion of proinflammatory cytokines (IL-6, TNF-α, and INF-γ) in PBMCs from healthy volunteers, underscoring their immune safety profile.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,607,"aODN-Survivin (recovered B2 from PMID:38672408, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,3. Results > 3.3. Intrinsic Toxicity and Transfection Efficiency of TRIFAPYs; paragraph 31,3903,Synthesis and Validation of TRIFAPYs as a Family of Transfection Agents for Therapeutic Oligonucleotides.,38672408,PMC11048556,10.3390/biom14040390,https://pubmed.ncbi.nlm.nih.gov/38672408/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"While the TRIFAPYs did not show significant toxicity by themselves at 1.5 µg/mL, the compounds containing alkyl chains from C12 through C18 showed a clear effect in decreasing cell viability when combined with the PPRH.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,608,unspecified siRNA (PMID:38617800),siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,A,Results > Biocompatibility Test of Different Scaffolds; paragraph 34,3912,Microdroplets Encapsulated with NFATc1-siRNA and Exosomes-Derived from MSCs Onto 3D Porous PLA Scaffold for Regulating Osteoclastogenesis and Promoting Osteogenesis.,38617800,PMC11015852,10.2147/IJN.S443413,https://pubmed.ncbi.nlm.nih.gov/38617800/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,609,unspecified siRNA (PMID:38613388),ASO,,,,,,,,,,,,unspecified,unspecified,renal,renal safety,B,Materials and methods > Animal experiments; paragraph 12,3913,Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.,38613388,PMC11109979,10.1093/nar/gkae260,https://pubmed.ncbi.nlm.nih.gov/38613388/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Mice injected with Chol-siRNAHTT/Htt and DCA-siRNAHTT/Htt exhibited phenotypic hallmarks of acute oligonucleotide-induced neurotoxicity,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,611,"vivo-3′UTR (recovered B2 from PMID:39676860, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Discussion; paragraph 31,10547,Effective inhibition of dengue virus replication using 3'UTR-targeted Vivo-Morpholinos.,39676860,PMC11638040,10.3389/fimmu.2024.1491230,https://pubmed.ncbi.nlm.nih.gov/39676860/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, there was no statistical difference in cell activity between the experimental groups and the control group at the same time point, indicating that different concentrations of drugs had no significant effect on cell viability.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,615,"HNP-siHOXB7 (recovered B2 from PMID:39458966, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,5. Conclusions; paragraph 51,10648,In Vivo HOXB7 Gene Silencing and Cotreatment with Tamoxifen for Luminal A Breast Cancer Therapy.,39458966,PMC11509954,10.3390/ph17101325,https://pubmed.ncbi.nlm.nih.gov/39458966/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,616,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,2. Materials and Methods > 2.3. Functional and Safety Assessments; paragraph 10,11036,Nusinersen Treatment for Spinal Muscular Atrophy: Retrospective Multicenter Study of Pediatric and Adult Patients in Kuwait.,38921951,PMC11206794,10.3390/neurolint16030047,https://pubmed.ncbi.nlm.nih.gov/38921951/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Overall, there were no serious adverse events related to nusinersen use in the pediatric cohort.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,622,patisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,immunotoxicity,immune activation,C,Discussion; paragraph 9,11357,Patisiran exposure in early pregnancy: a case report.,38532802,PMC10964446,10.1177/17562864241239755,https://pubmed.ncbi.nlm.nih.gov/38532802/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We describe here the first case of exposure to patisiran treatment, a small interfering RNA molecule, during early pregnancy of a 36-year-old woman with symptomatic hereditary transthyretin-related amyloidosis. There were no major complications during pregnancy and delivery, except for a postpartum hemorrhage due to uterine atony.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,623,fitusiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety; paragraph 27,11416,Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial.,38452197,PMC11181353,10.1182/blood.2023021864,https://pubmed.ncbi.nlm.nih.gov/38452197/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,625,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 62,11479,The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.,38383439,PMC10882889,10.1186/s12943-024-01955-7,https://pubmed.ncbi.nlm.nih.gov/38383439/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 38383439; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,627,siRNA-mediated,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,RESULTS AND DISCUSSION > Evaluation of the efficacy of gene silencing with in vitro RT-PCR; paragraph 45,12444,Investigation of the efficacy of siRNA-mediated KRAS gene silencing in pancreatic cancer therapy.,39553720,PMC11566511,10.7717/peerj.18214,https://pubmed.ncbi.nlm.nih.gov/39553720/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The siRNA/AuPEI cells in the application groups, assessed by the WST-1 technique, had a viability rate of over 90%, indicating no toxicity or side effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,628,"cRGD-GR9G-(LLHH)3/siEGFR/siP65 (recovered B2 from PMID:39539970, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Influence of Nanoparticles on Tumor Growth and Survival Time in Orthotopic Glioblastoma Mice and Its Evaluation of Immunogenicity and Toxicity; paragraph 53,12446,Stimuli-Responsive Peptide/siRNA Nanoparticles as a Radiation Sensitizer for Glioblastoma Treatment by Co-Inhibiting RELA/P65 and EGFR.,39539970,PMC11559232,10.2147/IJN.S483252,https://pubmed.ncbi.nlm.nih.gov/39539970/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 39539970; weak/generic or abstract-limited support for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,629,"cRGD-PEG-siRNA (recovered B2 from PMID:39431993, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > Toxicity of cRGD-PEG-siRNA to Renal Tubular Epithelial Cells; paragraph 11,12453,A pH-Sensitive cRGD-PEG-siRNA Conjugated Compound Targeting Glioblastoma.,39431993,PMC11583972,10.1021/acs.bioconjchem.4c00255,https://pubmed.ncbi.nlm.nih.gov/39431993/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Conversely, even at elevated concentrations, cRGD-PEG-siNC treatment did not significantly affect cell viability compared to the control group, except at 2000 nM where viability decreased to 90.03%.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,631,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and discussion > Inflammatory inhibition effect of the hybrid nanocomposite; paragraph 40,12500,"Carboxymethylcellulose encapsulated fingolimod, siRNA@ZnO hybrid nanocomposite as a new anti-Alzheimer's material.",39006767,PMC11240087,10.1039/d4ra01965b,https://pubmed.ncbi.nlm.nih.gov/39006767/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In the cell viability test in immortalized microglia cells (IMG), the hybrid nanocomposite (NP) exhibited no significant effect on cell survival after 48 hours of incubation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,634,"siIRF1 (recovered B2 from PMID:39629104, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,B,Abstract > Methods; paragraph 2,13678,T Lymphocyte-Macrophage Hybrid Membrane-Coated Biomimetic Nanoparticles Alleviate Myocarditis via Suppressing Pyroptosis by Targeting Gene Silencing.,39629104,PMC11614587,10.2147/IJN.S487598,https://pubmed.ncbi.nlm.nih.gov/39629104/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Cell viability remained stable at concentrations up to 40 μg/mL (Figure S3A–D), indicating their good biocompatibility.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,639,unspecified ASO (PMID:38042877),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Optimized BROTHERS architectures mitigate hepatotoxicity without affecting antisense activity; paragraph 11,1136,Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.,38042877,PMC10693639,10.1038/s41467-023-43714-0,https://pubmed.ncbi.nlm.nih.gov/38042877/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Throughout this period, there was no change in body weight or abnormal elevation in ALT levels in the BRO-treated arm (Fig. 2f, g).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,640,unspecified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,4. Materials and Methods > 4.8. Cytotoxicity Assay; paragraph 37,1292,Antiviral Efficacy of RNase H-Dependent Gapmer Antisense Oligonucleotides against Japanese Encephalitis Virus.,37834294,PMC10573891,10.3390/ijms241914846,https://pubmed.ncbi.nlm.nih.gov/37834294/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Other JEV-RNA-targeted and control LNA gapmers were not toxic in SK-N-SH cells at any concentration tested.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,641,unspecified ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract > Methods; paragraph 2,1955,"The exon-skipping oligonucleotide, KitStop, depletes tissue-resident mast cells in vivo to ameliorate anaphylaxis.",36798116,PMC9927222,10.3389/fimmu.2023.1006741,https://pubmed.ncbi.nlm.nih.gov/36798116/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No adverse effects were observed in either group and no change in body weight occurred for the duration of the treatment course ( Figure 3B ).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,642,unspecified siRNA (PMID:36727438),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,RESULTS > SH-BC-893 increases ASO delivery and activity in vitro; paragraph 20,1958,Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.,36727438,PMC9976930,10.1093/nar/gkad023,https://pubmed.ncbi.nlm.nih.gov/36727438/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In mice, oral administration of SH-BC-893 increased ASO potency in the liver by 15-fold without toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,643,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 24,11811,The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.,38077055,PMC10705697,10.21203/rs.3.rs-1297358/v3,https://pubmed.ncbi.nlm.nih.gov/38077055/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Mouse weight, a surrogate to assess potential treatment toxicity, remained stable over the course of therapy for Control ASO and T-RECS ASO in all cohorts (Fig.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,644,unspecified ASO (PMID:38015828),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Design of locked nucleic acid (LNA) ASO gapmers targeting Atp1a2; Fig 1 caption,11827,Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice.,38015828,PMC10683999,10.1371/journal.pone.0294731,https://pubmed.ncbi.nlm.nih.gov/38015828/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,646,"9b2KC-23b (recovered B2 from PMID:37744174, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > CPP-PMO antimiRs improve histopathology signs and muscle function in HSALR; paragraph 15,11931,Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression.,37744174,PMC10514136,10.1016/j.omtn.2023.09.001,https://pubmed.ncbi.nlm.nih.gov/37744174/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Finally, to check for possible CPP-PMO-mediated immune system activation, the bodyweight-normalized spleen weight (Figure S6A) and weight gain or loss (Figures S6B and S6C) were analyzed in each experimental group, with no significant between-group changes found.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,648,unspecified ASO (PMID:37704069),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,RESULTS > Effect of Notch3 ASOs on Notch3 Expression in Cells of the Osteoblast Lineage; paragraph 17,12175,Antisense oligonucleotides targeting a NOTCH3 mutation in male mice ameliorate the cortical osteopenia of lateral meningocele syndrome.,37704069,PMC10591917manuscript-id: NIHMS1931813,10.1016/j.bone.2023.116898,https://pubmed.ncbi.nlm.nih.gov/37704069/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The subcutaneous administration of Notch3 mutant ASO at 50 mg/Kg decreased Notch6691-TTATGA mRNA in bone without apparent toxicity;,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,650,"iLANDsiPAK4 (recovered B2 from PMID:37719367, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Synergistic antitumor effects in vivo; paragraph 29,13969,Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles.,37719367,PMC10501866,10.1016/j.apsb.2023.03.020,https://pubmed.ncbi.nlm.nih.gov/37719367/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In addition, no obvious histological toxicity and inflammation infiltrates were observed in major organs of mice, including the brain, heart, liver, spleen, lung, and kidney, after different treatments at the highest siRNA doses (Supporting Information Fig. S17).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,651,single-chain,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,renal,renal safety,B,Abstract; paragraph 1,13975,Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor.,37692001,PMC10483903,10.4103/JAPTR.JAPTR_117_23,https://pubmed.ncbi.nlm.nih.gov/37692001/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The results of the cytotoxicity assay demonstrated the CoV-2-RBD-1C aptamer’s excellent adaptability and, as a consequence, reflected its economic advantage due to low concentration could be used.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,652,inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Discussion; paragraph 14,14031,Painful and recurring injection site reaction to alirocumab and evolocumab in a young woman with familial hypercholesterolemia and effective therapeutic alternative based on inclisiran: a case report.,37424909,PMC10326624,10.3389/fcvm.2023.1181720,https://pubmed.ncbi.nlm.nih.gov/37424909/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No adverse events were reported after inclisiran administration and LDL-C levels decreased significantly, confirming the evidence that this innovative approach to hypercholesterolemia is a safe and effective resource in patients at high CV risk who cannot achieve LDL-C goal with conventional lipid-lowering therapies and antibody-based PCSK9i.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,654,"RO7062931 (recovered B2 from PMID:37147890, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,RESULTS > Safety; paragraph 27,14152,A single ascending dose study of single-stranded oligodeoxyribonucleotide RO7062931 in Chinese healthy volunteers.,37147890,PMC10339693,10.1111/cts.13531,https://pubmed.ncbi.nlm.nih.gov/37147890/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Adverse events (AEs) were reported in 22 of 33 (66.6%) RO7062931 recipients (n = 80 treatment‐related) and seven of eight (87.5%) placebo recipients (n = 1 treatment‐related). Apart from two moderate‐intensity AEs, all AEs were mild.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,656,inclisiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,DISCUSSION; paragraph 60,14195,The N-Acetylgalactosamine-conjugated small interfering RNA inclisiran can be coadministered safely with atorvastatin in cynomolgus monkeys resulting in additive low-density lipoprotein cholesterol reductions.,37021909,PMC10077952,10.1002/prp2.1080,https://pubmed.ncbi.nlm.nih.gov/37021909/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No toxicities or adverse effects were observed in any cohort receiving inclisiran, either alone or in combination.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,657,single-ascending,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,14202,"A multi-purpose Japanese phase I study in the global development of vupanorsen: Randomized, placebo-controlled, single-ascending dose study in adults.",37002654,PMC10175964,10.1111/cts.13498,https://pubmed.ncbi.nlm.nih.gov/37002654/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Vupanorsen was well‐tolerated with no treatment‐related adverse events reported for either dose.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,658,"DG9-PMO (recovered B2 from PMID:36719755, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,immunotoxicity,immune activation,A,Results > DG9-PMO treatment rescues the SMA phenotype without apparent toxicity.; paragraph 19,14276,DG9-conjugated morpholino rescues phenotype in SMA mice by reaching the CNS via a subcutaneous administration.,36719755,PMC10077475,10.1172/jci.insight.160516,https://pubmed.ncbi.nlm.nih.gov/36719755/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The treatment ameliorated the atrophic musculature and improved breathing function accompanied by improved muscle strength and innervation at the neuromuscular junction with no signs of apparent toxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,659,unspecified siRNA (PMID:36614194),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,2. Results > 2.6. CCK-BR Targeted NPs Exhibit Broad Safety Profile and Lack off Target Toxicity; paragraph 15,14302,Target-Specific Nanoparticle Polyplex Down-Regulates Mutant Kras to Prevent Pancreatic Carcinogenesis and Halt Tumor Progression.,36614194,PMC9821664,10.3390/ijms24010752,https://pubmed.ncbi.nlm.nih.gov/36614194/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Safety and toxicity studies were performed in immune competent mice after short or long-term exposure and showed no off-target toxicity by histological or biochemical evaluation.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,660,unspecified ASO (PMID:35861704),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,"Results > MsPA backbone improves potency, whereas gap2 OMe reduces toxicity in cytotoxic PS ASOs; FIG. 1. caption",1485,The Combination of Mesyl-Phosphoramidate Inter-Nucleotide Linkages and 2'-O-Methyl in Selected Positions in the Antisense Oligonucleotide Enhances the Performance of RNaseH1 Active PS-ASOs.,35861704,PMC9595634,10.1089/nat.2022.0005,https://pubmed.ncbi.nlm.nih.gov/35861704/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Even at the highest dose used (150 mg/kg), the gap2 OMe-modified ASO did not cause ALT/AST elevation.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,661,"ASO-001933 (recovered B2 from PMID:36090761, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Initial tiling screen identified a parental ASO targeting the 3′ UTR of MAPT with high cross-species reactivity; paragraph 6,1615,Identification and characterization of a MAPT-targeting locked nucleic acid antisense oligonucleotide therapeutic for tauopathies.,36090761,PMC9424863,10.1016/j.omtn.2022.07.027,https://pubmed.ncbi.nlm.nih.gov/36090761/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Mice treated with 100 μg of ASO-001933 ICV showed robust tau mRNA reduction by 80% 72 h post dosing and no obvious acute in vivo signs as indicated by a tolerability scores of <1 in a modified Irwin battery31 (Figure 2C).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,662,single-dose,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Single-dose tolerability study of lead ASO candidates in cynomolgus monkeys; paragraph 17,1617,"Developing antisense oligonucleotides for a TECPR2 mutation-induced, ultra-rare neurological disorder using patient-derived cellular models.",35860385,PMC9287140,10.1016/j.omtn.2022.06.015,https://pubmed.ncbi.nlm.nih.gov/35860385/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Histopathology analyses of brain, spinal cord (lumbar, thoracic, and cervical), and dorsal root ganglia tissues indicated that the single 20-mg dose of ASO-005-02, ASO-059, or ASO-066 to cynomolgus monkeys via intrathecal injection did not result in any test item-related gross or microscopic changes at study termination (Figure S11).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,664,"LNP-S60-siRNA (recovered B2 from PMID:36520934, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > LNP containing DSPS can reach the cytoplasm of cells without detectable cytotoxicity; paragraph 14,1964,Inhibition of c-Rel expression in myeloid and lymphoid cells with distearoyl -phosphatidylserine (DSPS) liposomal nanoparticles encapsulating therapeutic siRNA.,36520934,PMC9754606,10.1371/journal.pone.0276905,https://pubmed.ncbi.nlm.nih.gov/36520934/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"As shown in Fig 3B, the cell viability was not changed at the concentrations of LNP tested (0.1 to 50 μM). Similarly, insignificant levels of LDH release were detected in the supernatant of cultured cells, indicating that cells remained healthy following our treatment with LNP-S60 (Fig 3C).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,665,"PNA4986 (recovered B2 from PMID:35436109, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > Cell Toxicity of Dendron–PNAs; paragraph 13,1980,Antisense Peptide Nucleic Acid-Diaminobutanoic Acid Dendron Conjugates with SbmA-Independent Antimicrobial Activity against Gram-Negative Bacteria.,35436109,PMC9112330,10.1021/acsinfecdis.2c00089,https://pubmed.ncbi.nlm.nih.gov/35436109/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The compound was also well tolerated in mice upon i.v. administration up to a dose of 20 mg/kg, and in vivo fluorescence imaging indicated clearance via renal excretion with slight accumulation in the kidneys and liver.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,666,"IONIS-FXIRx (recovered B2 from PMID:35155859, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Safety; paragraph 28,1981,Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXI(Rx) in Patients With ESRD.,35155859,PMC8820988,10.1016/j.ekir.2021.11.011,https://pubmed.ncbi.nlm.nih.gov/35155859/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There was no detectable hepatotoxicity or effect on platelets, and no treatment-related changes were observed in hepatic function based on transaminases or severe thrombocytopenia.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,668,"ASO 5–2 (recovered B2 from PMID:34949835, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > PS reduction optimizes ASO5 safety and activity in mice; paragraph 15,2727,Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide.,34949835,PMC8861976manuscript-id: NIHMS1779498,10.1038/s41591-021-01557-6,https://pubmed.ncbi.nlm.nih.gov/34949835/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Neither ASO produced adverse behavioral side effects; all animals remained healthy until they were sacrificed at 21 days. Routine clinical blood chemistry and liver and kidney morphology after H&E staining revealed no gross abnormalities.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,670,unspecified siRNA (PMID:36457549),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Materials and Methods > The Cytotoxicity Studies of iRGD Functionalized Lipopolysaccharide-Amine Nanopolymersomes to Mesenchymal Stem Cells; paragraph 11,4051,Combined Self-Assembled iRGD Polymersomes for Effective Targeted siRNA Anti-Tumor Therapy.,36457549,PMC9707323,10.2147/IJN.S383862,https://pubmed.ncbi.nlm.nih.gov/36457549/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The introduced iRGD keeps tumor-targeting and -penetrating bioactivity, which endows iRGD-NPs with ~100% of tumor-cell uptake and excellent tumor spheroid-penetration, and thus iRGD-NPs can efficiently deliver siVEGF to significantly inhibit angiogenesis in zebrafish and tumor growth in nude mice bearing breast cancer without obvious toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,671,"HA-SeSe-COOH/siR-93C@PAMAM (recovered B2 from PMID:35156491, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and discussion > In vivo anticancer activity and safety evaluation; paragraph 49,4091,Hyaluronic acid-modified redox-sensitive hybrid nanocomplex loading with siRNA for non-small-cell lung carcinoma therapy.,35156491,PMC8856077,10.1080/10717544.2022.2032874,https://pubmed.ncbi.nlm.nih.gov/35156491/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"As a contrast, insignificant inflammation and negligible necrotic cells could be observed in HA-SeSe-COOH/siR-93C@PAMAM treated group, indicating that the outer layer HA-SeSe-COOH did significantly improve the biosafety of PAMAM.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,672,siRNA-Based,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,RESULTS AND DISCUSSION > Hairpin-like Design Increases Serum Nuclease Resistance and Decreases SNA Cytotoxicity.; paragraph 12,4092,Hairpin-like siRNA-Based Spherical Nucleic Acids.,35143189,PMC8938942manuscript-id: NIHMS1785508,10.1021/jacs.1c12750,https://pubmed.ncbi.nlm.nih.gov/35143189/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Indeed, the median lethal dose (LD50) occurs at a higher siRNA concentration with hairpin-like siRNA-SNAs than with hybridized siRNA-SNAs, indicating that the hairpin-like architecture is less cytotoxic.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,676,unspecified ASO (PMID:34921016),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > ASO1-cEt/DNA inhibits HCC cell growth; paragraph 29,14660,ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth.,34921016,PMC8898261manuscript-id: NIHMS1767244,10.1158/0008-5472.CAN-20-0948,https://pubmed.ncbi.nlm.nih.gov/34921016/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"During the three weeks of treatment, no obvious gross abnormalities were observed. Furthermore, we did not detect any histological abnormalities in the various organs in either mASO3-cEt/DNA-treated, Ctrl-cEt/DNA-treated, or saline-treated mice after three weeks of treatment (Fig. 6H). In a separate experiment, we assessed alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum collected from C57BL6 mice that were administered subcutaneous injections of either saline or mASO3-cEt/DNA at 100 mg/kg/wk for 4 weeks. We did not detect any significant difference in either of the transaminase plasma levels. Similar to mASO3-cEt/DNA treatment in FVB/N mice, the C57BL6 mice likewise did not show significant differences in organ weights or total body weight (Supplementary Fig. 8C–E). These observations indicate that mASO3-cEt/DNA is well tolerated in both wild-type FVB/N mice and C57BL6 mice.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,677,siRNA-Loaded,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,4. Discussion; paragraph 36,1635,Development of siRNA-Loaded Lipid Nanoparticles Targeting Long Non-Coding RNA LINC01257 as a Novel and Safe Therapeutic Approach for t(8;21) Pediatric Acute Myeloid Leukemia.,34683974,PMC8539450,10.3390/pharmaceutics13101681,https://pubmed.ncbi.nlm.nih.gov/34683974/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, in stark contrast to Kasumi-1 cells, where LNP-si-LINC01257 significantly decreased cell growth and viability, treatment with LNP-si-LINC01257 exerted a negligible impact on the viability of all three PBMC populations, with no difference in viability observed in monocytes and T cells, and a small but non-significant increase in B cell viability (Figure 6E and Figure S4B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,678,Site-specific,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,Abstract; paragraph 1,1638,"Site-specific Incorporation of 2',5'-Linked Nucleic Acids Enhances Therapeutic Profile of Antisense Oligonucleotides.",34141070,PMC8201499,10.1021/acsmedchemlett.1c00072,https://pubmed.ncbi.nlm.nih.gov/34141070/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Our results demonstrate that incorporation of 2′,5′-linked RNA in the gap region dramatically improved hepatotoxicity profile of PS-ASOs without compromising potency and provide a novel alternate chemical approach for improving therapeutic index of ASO drugs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,679,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > In Vivo Effects of NVP-13 on Target Regulation and Intracellular Pathways: NVP-13 is a Safe and Effective Compound in Cynomolgus Monkeys; paragraph 8,1645,Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling.,33860461,PMC8609055,10.1007/s13311-021-01045-2,https://pubmed.ncbi.nlm.nih.gov/33860461/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"NVP-13 was very well tolerated, with “No Observed Adverse Effect Level” up to 4 mg/animal.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,680,"IONIS-AGT-LRx (recovered B2 from PMID:34222719, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Discussion; paragraph 25,1992,Antisense Inhibition of Angiotensinogen With IONIS-AGT-L(Rx): Results of Phase 1 and Phase 2 Studies.,34222719,PMC8246029,10.1016/j.jacbts.2021.04.004,https://pubmed.ncbi.nlm.nih.gov/34222719/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"IONIS-AGT-LRx was well tolerated with no significant changes in platelet count, potassium levels, or liver and renal function.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,684,"peptide-siRNA-DOX (recovered B2 from PMID:34948105, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,5. Conclusions; paragraph 30,14708,Cell Penetrating Peptide-Based Self-Assembly for PD-L1 Targeted Tumor Regression.,34948105,PMC8703959,10.3390/ijms222413314,https://pubmed.ncbi.nlm.nih.gov/34948105/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In vivo, it shows good biocompatibility as there are no changes in mice’s body weight.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,686,"CpG2018B (recovered B2 from PMID:34566407, curator:CM)",CpG oligodeoxynucleotide,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Safety of Combined Therapy with CpG and the mRNA Vaccine; paragraph 28,14741,CpG Oligodeoxynucleotide Developed to Activate Primate Immune Responses Promotes Antitumoral Effects in Combination with a Neoantigen-Based mRNA Cancer Vaccine.,34566407,PMC8459178,10.2147/DDDT.S325790,https://pubmed.ncbi.nlm.nih.gov/34566407/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No gross pathological findings related to the mRNA vaccine or CpG were observed in the liver (Figure 5M).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,687,"MRCV-19 (recovered B2 from PMID:34440222, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,2. Materials and Methods > 2.4. Method for Measuring Cytotoxic Effect of Compounds; paragraph 9,14753,Vivo-Morpholino-Based Antiviral for SARS-CoV-2: Implications for Novel Therapies in the Treatment of Acute COVID-19 Disease.,34440222,PMC8394971,10.3390/biomedicines9081018,https://pubmed.ncbi.nlm.nih.gov/34440222/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In viability assays using MRCV-19 alone, we observed a high level of viability after cellular exposure to MRCV-19 at different concentrations (Figure 4). We observed low toxicity over 72 h post-exposure.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,690,sided,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general toxicity,toxicity,B,Abstract; paragraph 2,14789,Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance).,34251414,PMC8288671,10.1182/bloodadvances.2021004233,https://pubmed.ncbi.nlm.nih.gov/34251414/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No differences in toxicity were observed between arms.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,693,Site-specific,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,"RESULTS > Effect of site-specific incorporation of R- and S-5′-methyl DNA on duplex thermal stability, ASO activity and toxicity in cells; Figure 3. caption",14905,Site-specific incorporation of 5'-methyl DNA enhances the therapeutic profile of gapmer ASOs.,33544849,PMC7913697,10.1093/nar/gkab047,https://pubmed.ncbi.nlm.nih.gov/33544849/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Most of the R- and S-5′-methyl DNA modified ASOs exhibited comparable potency but significantly reduced toxicity even at the highest dose of 150 mg/kg, as compared to the parent ASO 558807 which can be lethal when administered at doses above 50 mg/kg (Figure 4A and B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,694,unspecified PMO (PMID:33337582),PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > PMO‐M improves muscle pathologies without detectable toxicity in mdx mice; paragraph 20,14926,MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice.,33337582,PMC7863382,10.15252/emmm.202012993,https://pubmed.ncbi.nlm.nih.gov/33337582/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Consistently, no morphological abnormality was found in kidney and liver (Fig 6C), indicating that PMO‐M does not cause any detectable toxicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,695,"NVP-13 (recovered B2 from PMID:32178467, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,2. Results > 2.1. Discovery Process; paragraph 7,1492,Antisense Oligonucleotide in LNA-Gapmer Design Targeting TGFBR2-A Key Single Gene Target for Safe and Effective Inhibition of TGFβ Signaling.,32178467,PMC7139664,10.3390/ijms21061952,https://pubmed.ncbi.nlm.nih.gov/32178467/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Body weight did not significantly change for any ASO candidate. X05134 (ALT: 64.9 U/l ± 21.0, AST: 108.9 ± 13.5), X07080 (ALT: 287.2 U/l ± 65.3, AST: 273.4 ± 101.3) and X07095 (ALT: 95.9 U/l ± 46.7, AST: 89.1 ± 21.8, Saline ALT: 9.9 ± 2.2, Saline AST: 28.2 ± 2.2) produced relevant liver enzyme elevations while X07070, X07085, X07091 = NVP-13 and X07065 did not affect ALT and AST levels compared to saline.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,696,"LNAc/2′OMe18h (recovered B2 from PMID:31873063, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Toxicity status of chimeric LNA/2′OMe ASOs in vivo; paragraph 34,1660,Systemic Evaluation of Chimeric LNA/2'-O-Methyl Steric Blockers for Myotonic Dystrophy Type 1 Therapy.,31873063,PMC7133450,10.1089/nat.2019.0811,https://pubmed.ncbi.nlm.nih.gov/31873063/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Assessment of liver sections revealed randomly distributed necrosis in ∼10% of hepatocytes in two mice injected with LNAc/2′OMe18h.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,700,unspecified ASO (PMID:32805488),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,"Results > MYC ASO Treatment Is Not Associated with Morbidity, Mortality, or Toxicity; paragraph 12",14986,MYC ASO Impedes Tumorigenesis and Elicits Oncogene Addiction in Autochthonous Transgenic Mouse Models of HCC and RCC.,32805488,PMC7452286,10.1016/j.omtn.2020.07.008,https://pubmed.ncbi.nlm.nih.gov/32805488/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"MYC ASO Treatment Is Not Associated with Morbidity, Mortality, or Toxicity We did not observe any toxicity-related morbidity or mortality in the treatment or control groups.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,702,unspecified ASO (PMID:30988454),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Evaluation of in vitro cytotoxicity of the 2′-F modified AOs; paragraph 10,2782,Systematic evaluation of 2'-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro.,30988454,PMC6465270,10.1038/s41598-019-42523-0,https://pubmed.ncbi.nlm.nih.gov/30988454/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In general, all 2′-F modified AOs did not show any significant cytotoxicity in comparison to the fully 2′-OMe-PS control (Fig. 6).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,703,Site-specific,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > A single MOP linkage at position 2 in the DNA gap reduces toxicity for multiple ASOs; paragraph 46,3148,Site-specific replacement of phosphorothioate with alkyl phosphonate linkages enhances the therapeutic profile of gapmer ASOs by modulating interactions with cellular proteins.,31034558,PMC6582325,10.1093/nar/gkz247,https://pubmed.ncbi.nlm.nih.gov/31034558/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, replacing even one PS-linkage at position 2 or 3 from the 5′-side of the DNA-gap with alkylphosphonates reduced or eliminated toxicity of several hepatotoxic gapmer ASOs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,705,unspecified siRNA (PMID:31375812),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Di-siRNA are safe and well-tolerated in mice; paragraph 21,4213,A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.,31375812,PMC6879195manuscript-id: NIHMS1533065,10.1038/s41587-019-0205-0,https://pubmed.ncbi.nlm.nih.gov/31375812/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Finally, a comprehensive blood chemistry panel showed no detectable changes at any time point, suggesting a systemic tolerability of Di-siRNA administration to the CNS (Supplementary Fig. 14). Overall, Di-siRNA injection in CSF was well tolerated in mice at the doses and time points tested.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,706,"IONIS-PKKRx (recovered B2 from PMID:30817230, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Phase I study results > Safety and tolerability; paragraph 45,12610,IONIS-PKK(Rx) a Novel Antisense Inhibitor of Prekallikrein and Bradykinin Production.,30817230,PMC6461157,10.1089/nat.2018.0754,https://pubmed.ncbi.nlm.nih.gov/30817230/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There were no serious or severe nonserious adverse events observed in the study. The most common treatment-emergent adverse event in both cohorts was mild injection site reactions [6 (50.0%) subjects in SAD cohort and 16 (64.0%) subjects in MAD cohort experienced at least one, all receiving IONIS-PKKRx].",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,708,"BMSP-PMO-GF (recovered B2 from PMID:31629961, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > BMSP-PMO-GF Does Not Evoke Any Overt Toxicity in Adult mdx Mice; paragraph 14,15084,Hexose Potentiates Peptide-Conjugated Morpholino Oligomer Efficacy in Cardiac Muscles of Dystrophic Mice in an Age-Dependent Manner.,31629961,PMC6807288,10.1016/j.omtn.2019.09.012,https://pubmed.ncbi.nlm.nih.gov/31629961/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Serum AST and ALT levels significantly declined (Figure 6A) and there was no change in creatinine and urea (Figure 6B) in BMSP-PMO-GF-treated adult mdx mice compared to untreated age-matched mdx controls, indicating no liver and kidney toxicities.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,717,"revusiran (recovered B2 from PMID:28129130, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,2323,Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate.,28129130,PMC5363199,10.1016/j.ymthe.2016.10.019,https://pubmed.ncbi.nlm.nih.gov/28129130/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Revusiran was generally well tolerated, with transient, mild to moderate injection site reactions the most common treatment-emergent adverse events.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,723,silk,CpG oligodeoxynucleotide,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,A,2. Materials and Methods > 2.10. Cytotoxicity study; paragraph 19,12648,Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.,28694238,PMC5942204manuscript-id: NIHMS892590,10.1016/j.actbio.2017.07.014,https://pubmed.ncbi.nlm.nih.gov/28694238/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,There was no significant difference between MS2 and MS2KN/CpG-STAT3siRNA spheres in terms of cytotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,727,"LNA-i-miR-221 (recovered B2 from PMID:27327137, curator:CM)",miRNA agomir,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > P27 is upregulated in mouse tissues after LNA-i-miR-221 treatment; paragraph 8,4239,Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates.,27327137,PMC5022129,10.1038/mtna.2016.36,https://pubmed.ncbi.nlm.nih.gov/27327137/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"All the recorded values confirmed the safety profile of LNA-i-miR-221 in monkeys, as shown by hematology, coagulation, liver and kidney parameters (see Supplementary Figure S5–S7).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,729,unspecified siRNA (PMID:27483025),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Mstn siRNA cholesterol conjugate shows dose-dependent and sustained knockdown of Mstn mRNA in muscle and in circulating protein levels; paragraph 7,12672,Silencing Myostatin Using Cholesterol-conjugated siRNAs Induces Muscle Growth.,27483025,PMC5023400,10.1038/mtna.2016.55,https://pubmed.ncbi.nlm.nih.gov/27483025/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"There was no evidence of liver toxicity or muscle damage at all doses examined, as determined by monitoring serum alanine transaminase (ALT)/aspartate transaminase (AST) and muscle creatine phosphokinase, respectively (data not shown).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,731,DUX4,PMO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results; paragraph 6,15206,Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics.,27378237,PMC5023379,10.1038/mt.2016.111,https://pubmed.ncbi.nlm.nih.gov/27378237/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,736,unspecified ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general toxicity,toxicity,B,Abstract > Methods; paragraph 2,4256,In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells.,24586944,PMC3931823,10.1371/journal.pone.0089659,https://pubmed.ncbi.nlm.nih.gov/24586944/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Exposure to LNA-i-miR-221 did not cause any significant behavioral changes or weight loss in animals. Histology did not reveal any organ damage or pathologic changes in the liver, kidney or heart tissues of treated mice (data not shown), which indicates that the treatment was not toxic.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,742,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,4288,An exocyclic methylene group acts as a bioisostere of the 2'-oxygen atom in LNA.,20886816,PMC2993159manuscript-id: NIHMS242039,10.1021/ja105875e,https://pubmed.ncbi.nlm.nih.gov/20886816/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The Methylene-cLNA ASO D1 and the R-Me-cLNA ASO D2 showed modest to no elevations in ALT levels at the highest does evaluated while the LNA ASO was toxic at the high dose.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,743,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,general safety,systemic safety/tolerability,B,PubMed abstract,1063,LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial.,41876647,,10.1038/s41591-026-04262-4,https://pubmed.ncbi.nlm.nih.gov/41876647/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for general safety/systemic safety/tolerability in single; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,754,siRNA-micelles,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,3333,Structurally-defined non-cationic docosahexaenoic acid based siRNA-micelles for safe and effective combinatorial glioblastoma therapy.,41443351,,10.1016/j.jconrel.2025.114568,https://pubmed.ncbi.nlm.nih.gov/41443351/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hepatic/hepatotoxicity in siRNA-micelles; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,759,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,4787,The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial.,42108271,,10.1038/s41591-026-04408-4,https://pubmed.ncbi.nlm.nih.gov/42108271/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in signals; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,812,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,1014,"AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: Two randomized phase I trials.",39798707,,10.1016/j.jhep.2024.12.046,https://pubmed.ncbi.nlm.nih.gov/39798707/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in single; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,813,inotersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,PubMed abstract,1161,Carcinogenicity assessment of inotersen in Tg.rasH2 mice and Sprague-Dawley rats: Implications for 2'-MOE antisense oligonucleotides.,39580013,,10.1016/j.yrtph.2024.105743,https://pubmed.ncbi.nlm.nih.gov/39580013/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in inotersen; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,819,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,1842,NF-kappa B Oligo DNA decoy provides 12 months of pain relief and disc height restoration for patients with chronic discogenic low back pain-a randomized clinical trial.,40280496,,10.1016/j.spinee.2025.04.021,https://pubmed.ncbi.nlm.nih.gov/40280496/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hepatic/hepatotoxicity in significant; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,829,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,PubMed abstract,3789,Shielding siRNA by peptide-based nanofibers: An efficient approach for turning off EGFR gene in breast cancer.,39733890,,10.1016/j.ijbiomac.2024.139219,https://pubmed.ncbi.nlm.nih.gov/39733890/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hepatic/hepatotoxicity in siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,830,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,3790,"Application of Strontium Chloride Hexahydrate to Synthesize Strontium-Substituted Carbonate Apatite as a pH-Sensitive, Biologically Safe, and Highly Efficient siRNA Nanocarrier.",39723844,,10.1021/acsabm.4c01319,https://pubmed.ncbi.nlm.nih.gov/39723844/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hepatic/hepatotoxicity in siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,903,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,1166,"SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers.",37497888,,10.1002/ajh.27015,https://pubmed.ncbi.nlm.nih.gov/37497888/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,905,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,4042,"A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis.",36513186,,10.1016/j.jhep.2022.11.025,https://pubmed.ncbi.nlm.nih.gov/36513186/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in single; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,909,single-dose,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,12017,First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection.,37524230,,10.1016/j.jhep.2023.07.026,https://pubmed.ncbi.nlm.nih.gov/37524230/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in single-dose; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,947,unspecified ASO (PMID:26855051),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,PubMed abstract,2807,"Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides.",26855051,,10.1016/j.jconrel.2016.02.007,https://pubmed.ncbi.nlm.nih.gov/26855051/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In toxicity analysis, some of the linkers induced lethal toxicities when they were injected at high concentrations (>600μM). These toxicities were attributed to decreased platelet levels in the blood, suggesting an interaction between cholesterol-conjugated ASO and platelets.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,950,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,B,PubMed abstract,15203,"Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.",27939059,,10.1016/S0140-6736(16)31408-8,https://pubmed.ncbi.nlm.nih.gov/27939059/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in nusinersen; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,952,AMO122,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,C,PubMed abstract sentence 5,4257,The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice.,24511611,,,https://pubmed.ncbi.nlm.nih.gov/24511611/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for general safety/cell viability/cytotoxicity in AMO122; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,958,SQY51,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,cell viability/cytotoxicity,B,Materials and methods > Cell viability assay; paragraph 31,1213,Systemic distribution of tricyclo-DNA antisense oligonucleotide following intratracheal instillation in the mouse.,41583579,PMC12828233,10.1093/narmme/ugag001,https://pubmed.ncbi.nlm.nih.gov/41583579/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"A single 25 mg/kg pulmonary dose was safe and well-tolerated, with no adverse structural or immune effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,966,"siRMSTN (recovered B2 from PMID:41041909, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Evaluation of the Toxicity and Safety of IVSA‐siRNA Targeting MSTN; paragraph 28,1776,Silencing Myostatin Using In Vivo Self-Assembled siRNA Protects Against Cancer- and Dexamethasone-Induced Muscle Atrophy.,41041909,PMC12836460,10.1002/adhm.202502186,https://pubmed.ncbi.nlm.nih.gov/41041909/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Biochemical markers for liver functions, including alanine transaminase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBIL), as well as indicators for cardiac and kidney injuries, such as lactate dehydrogenase (LDH) and serum creatinine (CREA) and blood urea nitrogen (BUN), showed no significant differences among all groups (Figure S6A, Supporting Information).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,969,"APGS (recovered B2 from PMID:41732207, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,"Results > IC50, time course, and viability analysis; paragraph 10",3251,"Design, validation, and functional impact of oligonucleotides for multigene silencing in Alzheimer's disease.",41732207,PMC12925542,10.1016/j.omtn.2026.102848,https://pubmed.ncbi.nlm.nih.gov/41732207/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Both ASOs demonstrated potent, concentration-dependent gene silencing with IC50 values in the picomolar to low-nanomolar range for at least 48 h post-transfection, with no cytotoxicity at therapeutic concentrations (Figures 3 and 4).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,974,"S9 (recovered B2 from PMID:41552385, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > S9-SNA ameliorated the phenotype of SBMA mice; paragraph 12,3301,An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.,41552385,PMC12804371,10.1016/j.omtn.2025.102802,https://pubmed.ncbi.nlm.nih.gov/41552385/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"No significant toxicity of SNA-modified siRNA, including defective mouse behavior or weight gain, or histological signs of neuroinflammation was evident in the SBMA and SCA3 mice, supporting the safety and tolerability of this CNS treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1039,unspecified siRNA (PMID:40737088),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Alkyl phosphonate at positions 6–7 enhances the therapeutic profile and reduces hepatotoxicity of Ttr and Marc1 siRNAs; paragraph 65,1497,Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.,40737088,PMC12309379,10.1093/nar/gkaf692,https://pubmed.ncbi.nlm.nih.gov/40737088/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We also demonstrate enhanced safety in mice, as evidenced by reduced ALT/AST elevation and the absence of histopathological changes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1043,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hematological,thrombocytopenia,A,Abstract > Results:; paragraph 3,1828,Rats subject to extracorporeal membrane oxygenation have improved cardiac function following anticoagulation and reversal with factor IXa aptamer-antidote oligonucleotide pair.,40599554,PMC12208382,10.1097/CP9.0000000000000122,https://pubmed.ncbi.nlm.nih.gov/40599554/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hematological/thrombocytopenia in similar; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1057,Single-dose,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general toxicity,toxicity,A,RESULTS > Lead MECP2-targeting siRNAs tune MECP2 levels in wildtype mice for up to four months; paragraph 16,3701,Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model.,40313754,PMC12045366,10.21203/rs.3.rs-6465542/v1,https://pubmed.ncbi.nlm.nih.gov/40313754/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"produced no overt toxicity, though this study was not designed to detect subtle behavioral changes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1060,Single-dose,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,A,RESULTS > Single injection of non-isoform selective 1764_S1 but not E1 selective 112_S1 induces mixed behavioral effects in Tg1 mice; paragraph 36,3717,Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model.,40196492,PMC11974818,10.1101/2025.03.26.645328,https://pubmed.ncbi.nlm.nih.gov/40196492/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"These behavioral differences in 1764_S1, but not 112_S1 treated Tg1 mice may indicate adverse effects due to exaggerated pharmacological activity of the siRNA.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1083,BHF7,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Methods > Lactate dehydrogenase cytotoxicity assay; paragraph 31,8415,Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure.,40928446,PMC12790151,10.1016/j.jacbts.2025.101364,https://pubmed.ncbi.nlm.nih.gov/40928446/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,This demonstrated that BHF7 does not induce a cytotoxic response either in vitro or ex vivo.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1087,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,general safety,cell viability/cytotoxicity,C,Results and Discussion > Uptake and Conditional Gene Silencing in 3D Spheroids; paragraph 19,8595,Reconfigurable Nucleic Acid Nanoparticles with Therapeutic RNAi Responses to Intracellular Disease Markers.,40852577,PMC12369976manuscript-id: NIHMS2101912,10.1002/adfm.202508122,https://pubmed.ncbi.nlm.nih.gov/40852577/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,with cells dying due to uptake of recNANPs at less than 1%.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1117,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Stk25-Targeting ASO Therapy Hinders the Development and Progression of MASH-Related HCC in a Mouse Model; paragraph 16,10025,Therapeutic Potential of STE20-Type Kinase STK25 Inhibition for the Prevention and Treatment of Metabolically Induced Hepatocellular Carcinoma.,40024534,PMC12022666,10.1016/j.jcmgh.2025.101485,https://pubmed.ncbi.nlm.nih.gov/40024534/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"plasma concentrations of alanine transaminase (ALT) and aspartate aminotransferase (AST), the most widely used clinical biomarkers of MASH, were downregulated in mice dosed with Stk25-targeting ASOs compared with mice in the control groups",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1124,the ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,C,Results and Discussion > Gene Silencing Effects of the ASO/CDs; paragraph 39,10126,Nanodot-Inspired Precise Bacterial Gene Suppression in a Smart Hydrogel Bandage for Underwater Wound Healing.,39950874,PMC11967816,10.1002/advs.202415169,https://pubmed.ncbi.nlm.nih.gov/39950874/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Considerably high cell viabilities after their incubation for 24 h with CSGC and HepG2 cells were obtained (Figure S18,b, Supporting Information), consistent with the low cytotoxicity of the ASO/CDs‐hydrogel composite (Figure S18c, Supporting Information).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1131,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,renal,renal safety,A,2. Results > 2.7. In Vivo Anticancer Activity and Safety Evaluation; paragraph 16,12392,"Cetuximab-Immunoliposomes Loaded with TGF-β1 siRNA for the Targeting Therapy of NSCLC: Design, and In Vitro and In Vivo Evaluation.",39940962,PMC11818693,10.3390/ijms26031196,https://pubmed.ncbi.nlm.nih.gov/39940962/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for renal/renal safety in siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1141,"siTMEM45A (recovered B2 from PMID:39910045, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Construction and characterization of the BRCA primary cell-derived engineered exosomes; paragraph 14,13436,TMEM45A enhances palbociclib resistance and cellular glycolysis by activating AKT/mTOR signaling pathway in HR+ breast cancer.,39910045,PMC11799145,10.1038/s41420-025-02336-9,https://pubmed.ncbi.nlm.nih.gov/39910045/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To determine whether engineered exosomes have any side effects in vivo, we collected blood samples at the end of the PDX experiment for the detection of ALT, AST, BUN, and CREA. The results showed no significant differences between groups, and there were also no obvious statistical differences in the body weight of mice across the groups (Fig. S7A-D). Major organs from the mice were also collected and subjected to HE staining at the end of the experiment, as shown in Fig.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1156,unspecified siRNA (PMID:38192611),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > The structure and chemical configuration of the siRNA affects the distribution pattern in mouse retinas; paragraph 7,3958,Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in mouse and pig photoreceptors.,38192611,PMC10772295,10.1016/j.omtn.2023.102088,https://pubmed.ncbi.nlm.nih.gov/38192611/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To evaluate safety, we performed electroretinogram (ERG) recordings under scotopic (rod PR cell response) and photopic (cone PR cell response) conditions, which revealed no significant differences among the different dose groups (Figures 3C and S2). Similarly, immunohistochemical analyses of retinal cross-sections detected no migration of microglia marked by ionized calcium binding adaptor molecule 1 (Iba1) into the ONL and/or inner outer segment region, except for occasional cells at the highest dose (60 μg; arrowheads, Figure 3D). Consistent with this, there was no reactive gliosis in the retina as assessed by the normal expression of glial fibrillary acidic protein (GFAP) (Figure 3E).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1161,givosiran,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,3. Results > 3.4. Safety > Adverse Events; paragraph 37,10566,German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran.,39597922,PMC11594983,10.3390/jcm13226779,https://pubmed.ncbi.nlm.nih.gov/39597922/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Renal AEs included an early but transient moderate increase in serum creatinine (30.7%) or a reduction in the eGFR (11.5%, Table 2). In total, 15.4% of patients experienced a mild elevation of liver enzyme activities (<1.5 UNL, [AST/ALT]), with a further 7.7% of patients’ liver enzyme activities elevated further (>1.5ULN, [AST/ALT]). There were no episodes of pancreatitis.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1172,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,RESULTS > Extensive screening identifies a potent chemically stabilized SOD1-targeting siRNA; paragraph 11,10988,RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.,38979291,PMC11230209,10.1101/2024.06.20.599943,https://pubmed.ncbi.nlm.nih.gov/38979291/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To determine if SOD1 reduction by di-siRNASOD1_123 exNA in G93A mice impacted neurogliosis, we evaluated astrocyte and microglial morphology in the cortex and spinal cord. In the cortex, there was no evidence of either astrogliosis (Figure S3A,C) or microgliosis (Figure S4A,C) between wild-type, transgenic non-mutant or transgenic mutant untreated mice, while both phenomena were enhanced in di-siRNASOD1_123 exNA treated G93A mice. By contrast, in the lumbar spinal cord, untreated G93A mice exhibit both astrogliosis (Figure S3B,D) and microgliosis (Figure S4B,D) compared to wild-type or non-mutant transgenic mice that was unaffected by the di-siRNASOD1_123 exNA treatment. Taken together, these immunohistochemistry findings suggest that di-siRNASOD1_123 exNA treatment maintains synapse structure and protects against the synapse loss observed in untreated ALS mice.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1179,"OA2-siRAPSYN (recovered B2 from PMID:38741123, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Materials and methods > Cell viability assay; paragraph 15,11191,Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN.,38741123,PMC11089668,10.1186/s12951-024-02505-5,https://pubmed.ncbi.nlm.nih.gov/38741123/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Meanwhile, body weight of the mice did not have significant changes, and no adverse effects were noticeably observed during and after the treatments (Fig.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1180,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,B,Abstract > Methods; paragraph 2,11199,A Post-Marketing Surveillance Study of Nusinersen for Spinal Muscular Atrophy in Routine Medical Practice in China: Interim Results.,38722537,PMC11213752,10.1007/s12325-024-02852-7,https://pubmed.ncbi.nlm.nih.gov/38722537/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for general safety/systemic safety/tolerability in nusinersen; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1198,"siRNA‐CaP@PD1‐NVs (recovered B2 from PMID:38973319, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion > Multifunctional Validation of siRNA‐CaP@PD1‐NVs In Vitro; paragraph 15,13888,Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.,38973319,PMC11425963,10.1002/advs.202400951,https://pubmed.ncbi.nlm.nih.gov/38973319/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To further evaluate the in vivo toxicity of siPDL1‐CaP@PD1‐NVs, the serum and major organs (heart, liver, spleen, lung, kidney) were collected from the mice in different groups. H&E staining of important organs showed no obvious tissue morphological changes and intact cell morphology with distinct nucleus and cytoplasm (Figure S20, Supporting Information). Additionally, the serum biochemical markers also showed no significant change in any groups (Figure S21, Supporting Information). The results indicated that siPDL1‐CaP@PD1‐NVs possessed excellent in vivo safety with negligible side effects.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1203,unspecified ASO (PMID:37200862),ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > RNA-seq reveals activation of the interferon response by all ASOs and additional off-target effects on gene expression by the repeat gapmer; paragraph 19,1481,Block or degrade? Balancing on- and off-target effects of antisense strategies against transcripts with expanded triplet repeats in DM1.,37200862,PMC10185704,10.1016/j.omtn.2023.04.010,https://pubmed.ncbi.nlm.nih.gov/37200862/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Overall, interferon signaling appeared to be similarly induced by all ASOs, while interleukin signaling was more prominent for the repeat gapmer and control gapmer (Figure 3A).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1214,"si3033 (recovered B2 from PMID:37925520, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > si3033 has a good safety profile and enables JAK1 silencing in mouse skin over 5 weeks; paragraph 11,3979,Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.,37925520,PMC10625637,10.1038/s41467-023-42714-4,https://pubmed.ncbi.nlm.nih.gov/37925520/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Blood chemistry and CBC profiles were similar between si3033 and PBS-injected mice except there was a transient decrease of platelet counts in the siRNA-treated mice (Fig. 3c).,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1220,inotersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,general safety,systemic safety/tolerability,B,PubMed abstract,11924,Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy.,37768671,PMC10540057,10.1001/jama.2023.18688,https://pubmed.ncbi.nlm.nih.gov/37768671/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1240,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Materials and methods > Animal studies > Study 1; paragraph 15,1619,ANGPTL4 silencing via antisense oligonucleotides reduces plasma triglycerides and glucose in mice without causing lymphadenopathy.,35667416,PMC9270256,10.1016/j.jlr.2022.100237,https://pubmed.ncbi.nlm.nih.gov/35667416/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In separate experiments, injection of two different doses of ANGPTL4 ASO over 20 weeks of high-fat feeding reduced hepatic and adipose ANGPTL4 levels but did not trigger mesenteric lymphadenopathy, an acute phase response, chylous ascites, or any other pathological phenotypes.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1244,"SMN7D(-10-29) AO (recovered B2 from PMID:35464859, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,"Results > PMOs, or Double-Stranded 2′ O-methyl Phosphorothioate AOs, Do Not Form Nuclear Inclusions, Protecting From Cellular Toxicity and Off-Target Transcript Effects; paragraph 53",2210,"Single Stranded Fully Modified-Phosphorothioate Oligonucleotides can Induce Structured Nuclear Inclusions, Alter Nuclear Protein Localization and Disturb the Transcriptome In Vitro.",35464859,PMC9019733,10.3389/fgene.2022.791416,https://pubmed.ncbi.nlm.nih.gov/35464859/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1247,"PC-DCA siRNA (recovered B2 from PMID:35847173, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Systematic chemical optimization of sFLT1-targeting siRNAs improves placental accumulation and degree of sFLT1 silencing with a better safety profile; paragraph 30,4069,Chemical optimization of siRNA for safe and efficient silencing of placental sFLT1.,35847173,PMC9263991,10.1016/j.omtn.2022.06.009,https://pubmed.ncbi.nlm.nih.gov/35847173/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The advanced siRNA did not stimulate IL-6 levels but caused a non-significant increase in IL-12 levels (IL-6: 0.8, IL-12: 1.7) (Figure 8B).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1257,inotersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hematological,thrombocytopenia,A,RESULTS > Safety and tolerability; paragraph 21,14599,Real-life experience with inotersen in hereditary transthyretin amyloidosis with late-onset phenotype: Data from an early-access program in Italy.,35289020,PMC9314115,10.1111/ene.15325,https://pubmed.ncbi.nlm.nih.gov/35289020/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"A significant decrease in platelet count (p = 0.001, Friedman test) was observed from baseline to month 6 (M6), but no patient permanently discontinued the treatment because of this reason and no severe thrombocytopenia (<50.000 per cubic millimeter) occurred.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1263,Single-Stranded,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > Safety and Tolerability; FIG. 3 caption,1996,Clinical Study of Single-Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B.,34037271,PMC9291828,10.1002/hep.31920,https://pubmed.ncbi.nlm.nih.gov/34037271/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in Single-Stranded; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1270,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,Results > In vitro cytotoxicity assay; paragraph 10,12553,A smart multiantenna gene theranostic system based on the programmed assembly of hypoxia-related siRNAs.,34172725,PMC8233311,10.1038/s41467-021-24191-9,https://pubmed.ncbi.nlm.nih.gov/34172725/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->A: PMID 34172725; full-text grounding and high confidence outweighed the conservative v2 grade for hepatic/hepatotoxicity.,2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1289,"Pip6a-PMO (recovered B2 from PMID:31479430, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,C,Results and Discussion; paragraph 10,4212,Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice.,31479430,PMC6819114,10.1172/JCI128205,https://pubmed.ncbi.nlm.nih.gov/31479430/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Furthermore, mild histological changes observed in liver or kidney 2 weeks after Pip6a-PMO injections were mostly reversed 6 months later (Supplemental Table 5), supporting transient and reversible side effects of Pip6a-PMO treatment.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1292,"RGD-PEG-ECO/siβ3 (recovered B2 from PMID:31140918, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,Abstract; paragraph 1,12604,Formulation of Biocompatible Targeted ECO/siRNA Nanoparticles with Long-Term Stability for Clinical Translation of RNAi.,31140918,PMC6686697,10.1089/nat.2019.0784,https://pubmed.ncbi.nlm.nih.gov/31140918/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The frozen RGD-PEG-ECO/siβ3 nanoparticle formulation exhibits excellent biocompatibility, with no adverse effects on hemocompatibility and minimal immunogenicity.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1293,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hepatic,hepatotoxicity,A,RESULTS > Lipid-hsiRNAs elicit sustained systemic in vivo gene silencing after a single injection > Liver; paragraph 26,12616,Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways.,30535404,PMC6379714,10.1093/nar/gky1232,https://pubmed.ncbi.nlm.nih.gov/30535404/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We did not observe any variability in biomarkers of kidney toxicity, including blood urea nitrogen and creatinine levels (Supplementary Figure S5).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1297,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,A,Results > Identification of Lead Oligonucleotide Targeting the CEP290 c.2991+1655A>G Mutation; paragraph 6,12621,Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.,30114557,PMC6092551,10.1016/j.omtn.2018.07.010,https://pubmed.ncbi.nlm.nih.gov/30114557/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In a single dose setting of 900 μg per eye, QR-110 was well tolerated for up to 28 days, and no adverse findings related to QR-110 were observed (Figure S4).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1306,"MORF1-MORF2 (recovered B2 from PMID:24308267, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,MATERIALS AND METHODS > In vivo anticancer efficacy; paragraph 31,4261,Cell surface self-assembly of hybrid nanoconjugates via oligonucleotide hybridization induces apoptosis.,24308267,PMC3908873manuscript-id: NIHMS548399,10.1021/nn4053827,https://pubmed.ncbi.nlm.nih.gov/24308267/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Importantly, histology suggested no toxicity caused by the treatments in any of the tissues evaluated; this corresponded to a stable body weight growth of the treated animals (Supplementary Figure S13).",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1317,unspecified siRNA (PMID:41797405),siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,1737,Lung-Accumulating Mucin 5AC Silencing by Noninflammatory Lipid Nanoparticles for Asthma Treatment.,41797405,,10.1021/acsnano.5c16693,https://pubmed.ncbi.nlm.nih.gov/41797405/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"After three rounds of screening-evaluating gene silencing efficiency (in vitro and in vivo), LNP physicochemical properties and biosafety─we identify a lead candidate formulation (Formulation 1) that achieves 85% MUC5AC silencing efficiency in vivo, outperforming the integrin αvβ6 ligand-modified siRNA (69%), and demonstrates notably improved biosafety when compared to SM102 LNPs and MC3 LNPs.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1329,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,4516,"The small interfering RNA imdusiran as single and multiple doses in healthy, randomised individuals and non-randomised individuals with chronic hepatitis B (AB-729-001): a phase 1a/b trial.",42173110,,10.1016/S2468-1253(26)00058-0,https://pubmed.ncbi.nlm.nih.gov/42173110/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in single; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1387,"unspecified siRNA (v1 extraction artefact, pending source re-verification)",siRNA,,,,,,,,,,,,unspecified,unspecified,hepatic,hepatotoxicity,B,PubMed abstract,1478,"Durability and efficacy of solbinsiran, a GalNAc-conjugated siRNA targeting ANGPTL3, in adults with mixed dyslipidaemia (PROLONG-ANG3): a double-blind, randomised, placebo-controlled, phase 2 trial.",40179932,,10.1016/S0140-6736(25)00507-0,https://pubmed.ncbi.nlm.nih.gov/40179932/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hepatic/hepatotoxicity in siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
toxicity,toxicity_endpoint,1388,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,intraocular pressure spike / ocular safety,B,PubMed abstract sentence 3,3960,"Silencing of ocular transthyretin, a gene responsible for hereditary transthyretin amyloidosis, by intravitreal injection of an siRNA conjugate into rabbit eyes.",38157582,,10.1016/j.bbrc.2023.149397,https://pubmed.ncbi.nlm.nih.gov/38157582/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Intravitreal TTR siRNA conjugate safety is directly evaluated with an observed IOP spike; abstract support so Grade B."", ""grounding_quote"": ""This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes. Rabbit (r) TTR siRNA is a screened TTR siRNA conjugate from 53 candidates. The intraocular pressure (IOP) immediately after injection was high despite the 65.9 % decrease of aqueous humor TTR protein levels in the rTTR siRNA group compared with those in the Control siRNA group 2 weeks after the 50 μL siRNA injection."", ""source_pmid"": ""38157582"", ""candidate_domain"": ""toxicity""}",2026-06-07T21:51:24.380303+00:00
toxicity,toxicity_endpoint,1389,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,no adverse effects in chronic rodent dosing,C,PubMed abstract sentence 6,4253,Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing.,25434769,,10.1021/ja505986a,https://pubmed.ncbi.nlm.nih.gov/25434769/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""GalNAc-siRNA chronic dosing reports no adverse effects in rodents; generic abstract support so Grade C."", ""grounding_quote"": ""This enabled the SC administration of siRNA-GalNAc conjugates at therapeutically relevant doses and, importantly, at dose volumes of ≤1 mL. Chronic weekly dosing resulted in sustained dose-dependent gene silencing for over 9 months with no adverse effects in rodents."", ""source_pmid"": ""25434769"", ""candidate_domain"": ""toxicity""}",2026-06-07T21:51:24.380303+00:00
toxicity,toxicity_endpoint,1390,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,chemical-modification off-target reduction,C,PubMed abstract sentence 7,1003,siRMSD: A Structural Parameter to Reduce Sequence-Dependent Off-Target Effects for siRNA Design with Chemical Modifications.,40877521,,10.1007/978-1-0716-4742-4_24,https://pubmed.ncbi.nlm.nih.gov/40877521/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Chemical-modification-induced siRNA structural distortion is linked to reduced off-target effect; generic abstract support so Grade C."", ""grounding_quote"": ""Here, we introduce small interfering RNA root-mean-square deviation (siRMSD), a novel parameter that quantifies structural distortions induced by chemical modifications in siRNAs. We demonstrate a strong correlation between deviations from the canonical A-form RNA structure and the reduction in siRNA off-target effect."", ""source_pmid"": ""40877521"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.380303+00:00
toxicity,toxicity_endpoint,1391,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,PANAC GalNAc-siRNA conjugation improves gene silencing,C,PubMed abstract sentence 3,1049,General Platform for Efficient and Modular Assembly of GalNAc-siRNA Conjugates via Primary Amines and o-Nitrobenzyl Alcohol Cyclization Photoclick Chemistry Enabling Rapid Access to Therapeutic Oligonucleotides.,40151235,PMC11938030,10.1021/jacsau.5c00012,https://pubmed.ncbi.nlm.nih.gov/40151235/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""PANAC chemistry creates GalNAc-siRNA conjugates with superior gene-silencing effect; generic support so Grade C."", ""grounding_quote"": ""Leveraging the advantages of PANAC photoclick chemistry and modular conjugation linkers, our method enables the direct assembly of trivalent GalNAc (tGalNAc) with commercially available primary-amine-modified siRNAs. This approach demonstrates the efficient and rapid assembly of therapeutically relevant oligonucleotides with ligands of interest, offering operational simplicity and practicality; thus, it effectively overcomes the limitations of existing methods. More importantly, the developed siRNA–tGalNAc conjugates showed a robust gene silencing effect superior to the parent siRNA conjugate"", ""source_pmid"": ""40151235"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1392,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,2-prime ribose modification improves silencing and reduces off-targets,C,PubMed abstract sentence 1,1154,2'-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs.,41646886,PMC12870468,10.1016/j.omtn.2026.102835,https://pubmed.ncbi.nlm.nih.gov/41646886/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Designed 2-prime ribose modifications change siRNA stability, silencing activity, and off-target effects; generic support so Grade C."", ""grounding_quote"": ""following the substitution of the conventional 2′-O-methyl or 2′-O-fluoro ribose modifications with our newly designed functional groups, although the thermal stability of the duplexes decreased, the in vitro silencing activity against proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was significantly enhanced and the off-target effects of specific genes could be effectively mitigated"", ""source_pmid"": ""41646886"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1393,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,seed-region modification reduces off-target binding,C,PubMed abstract sentence 1,1157,An siRMSD parameter of structural distortion induced by chemical modification is predictive of the off-target effect of siRNA.,41467115,PMC12744844,10.1016/j.omtn.2025.102693,https://pubmed.ncbi.nlm.nih.gov/41467115/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Seed-region chemical modifications are shown to alter AGO2-bound structure and off-target binding; generic support so Grade C."", ""grounding_quote"": ""Here, we show that structural distortions caused by chemical modifications determine off-target effects. Modifications, including 2′-O-methoxyethyl, 2′-O-methyl, and 2′-formamido, at positions 2–5 disrupted the A-form RNA duplex on argonaute 2, preventing stable binding to target mRNA."", ""source_pmid"": ""41467115"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1394,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,LNA modification alters antiviral oligonucleotide activity,C,PubMed abstract sentence 10,1210,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1.,41704705,PMC12907196,10.3389/fmed.2026.1719202,https://pubmed.ncbi.nlm.nih.gov/41704705/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""PS/LNA oligonucleotide modification status is linked to measured antiviral IC50 changes; generic support so Grade C."", ""grounding_quote"": ""Variations in the 50% inhibitory viral reproductive dose (IC50) values among the oligonucleotides were observed, depending upon both the target and the incorporated LNA modification. Optimal IC50 values (90 ± 10 nM) were achieved using a PS oligonucleotide lacking LNA modifications, which targeted the HIV-1 integrase-encoding genomic region. Optimal HIV inhibitory action among LNA constructs was observed in an oligonucleotide with a 5’-end LNA modification targeting the HIV integrase region (IC50 = 1.12 ± 0.03 μM). The introduction of LNA modifications to PS oligonucleotides failed to enhance antiviral activity"", ""source_pmid"": ""41704705"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1395,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,scpBNA/scpBNA2 nuclease-stability and activity profile,C,PubMed abstract sentence 2,1408,"Cycloalkane Incorporation Into the 2',4'-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides.",41169576,PMC12569656,10.1021/jacsau.5c01005,https://pubmed.ncbi.nlm.nih.gov/41169576/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Cycloalkane-bridged BNA/LNA chemistry maintains ASO activity with reduced PS modification; generic support so Grade C."", ""grounding_quote"": ""Both scpBNA- and scpBNA2-modified ASOs exhibited antisense activity comparable to that of their 2′,4′-BNA/LNA-modified counterparts, maintaining activity even with reduced PS modifications in the scpBNA- or scpBNA2-modified regions"", ""source_pmid"": ""41169576"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1396,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,nucleobase modification reduces ASO hepatotoxicity,C,PubMed abstract sentence 2,1409,Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.,35801870,PMC9303313,10.1093/nar/gkac562,https://pubmed.ncbi.nlm.nih.gov/35801870/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Nucleobase modifications in gapmer ASOs are experimentally linked to reduced hepatotoxicity; generic support so Grade C."", ""grounding_quote"": ""In this study, we introduced single or multiple combinations of 17 nucleobase derivatives, including four novel derivatives, into hepatotoxic locked nucleic acid gapmer ASOs and examined their effects on hepatotoxicity. The results demonstrated successful identification of chemical modifications that strongly reduced the hepatotoxicity of gapmer ASOs."", ""source_pmid"": ""35801870"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1397,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,GalNAc3 conjugation potency increase,B,PubMed abstract sentence 4,1465,"Safety, Pharmacokinetic, and Pharmacodynamic Evaluation of a 2'-(2-Methoxyethyl)-D-ribose Antisense Oligonucleotide-Triantenarry N-Acetyl-galactosamine Conjugate that Targets the Human Transmembrane Protease Serine 6.",33431610,,10.1124/jpet.120.000222,https://pubmed.ncbi.nlm.nih.gov/33431610/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""GalNAc3 conjugation is linked to improved ASO potency and lower exposure; ISIS 702843 abstract support so Grade B."", ""grounding_quote"": ""A significant advancement in improving uptake into cells has come through the conjugation of ASOs to triantenarry N-acetyl-galactosamine (GalNAc3), a ligand for the asialoglycoprotein receptor on hepatocytes. The impact for antisense oligonucleotides, which are already taken up into hepatocytes, is a 10-fold improvement in potency in mice and up to a 30-fold potency improvement in humans, resulting in overall lower effective dose and exposure levels."", ""source_pmid"": ""33431610"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1398,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,alkyl phosphonate seed modification improves specificity,C,PubMed abstract sentence 2,1497,Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.,40737088,PMC12309379,10.1093/nar/gkaf692,https://pubmed.ncbi.nlm.nih.gov/40737088/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Single alkyl phosphonate seed-region modification improves specificity and reduces off-target effects; generic support so Grade C."", ""grounding_quote"": ""siRNAs modified with a single alkyl phosphonate linkage demonstrated enhanced specificity and therapeutic profile compared to the parent siRNA. We found that these modifications are most effective when positioned at the internucleotide linkages 6–7 from the 5′-end of the guide strand. Our findings reveal that siRNAs with this modification maintain robust on-target activity both in vitro and in vivo. Importantly, differential gene expression (DGE) analysis showed a significant reduction in off-target effects across in vitro and in vivo, leading to an improved therapeutic profile."", ""source_pmid"": ""40737088"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.381331+00:00
toxicity,toxicity_endpoint,1399,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,GNA isonucleotides improve activity/off-target profile,C,PubMed abstract sentence 1,2309,Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs.,34648028,PMC8565336,10.1093/nar/gkab916,https://pubmed.ncbi.nlm.nih.gov/34648028/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""GNA isonucleotide chemistry improves GalNAc-siRNA activity and off-target profile; generic support so Grade C."", ""grounding_quote"": ""Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile"", ""source_pmid"": ""34648028"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.382335+00:00
toxicity,toxicity_endpoint,1400,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,3' terminal 2'-O-methyl activity reduction,C,PubMed abstract sentence 3,2762,2'-O-Methyl at 20-mer Guide Strand 3' Termini May Negatively Affect Target Silencing Activity of Fully Chemically Modified siRNA.,32610253,PMC7327867,10.1016/j.omtn.2020.05.010,https://pubmed.ncbi.nlm.nih.gov/32610253/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""3' terminal 2'-O-methyl modification changed siRNA silencing activity; generic abstract evidence so Grade C."", ""grounding_quote"": ""Here, we systematically evaluated the impact of 3′ terminal modifications (2′-O-methyl versus 2′-fluoro) on guide strands of different length and showed that 3′ terminal 2′-O-methyl modification negatively impacts activity for >60% of siRNA sequences tested but only in the context of 20- and not 19- or 21-nt-long guide strands."", ""source_pmid"": ""32610253"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.382335+00:00
toxicity,toxicity_endpoint,1401,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,VHP peptide modification targeted siRNA-exosome delivery,B,PubMed abstract sentence 4,3325,Endothelial-targeted modification of ginseng-derived exosomes for IL-6 SiRNA delivery ameliorates hepatic ischemia-reperfusion injury.,41491215,PMC12781530,10.1186/s12951-025-03954-2,https://pubmed.ncbi.nlm.nih.gov/41491215/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""VHP modification of siRNA-loaded exosomes improved endothelial targeting and delivery; abstract support so Grade B."", ""grounding_quote"": ""VHP modification facilitated the targeted delivery of siRNA@VG-Exos to damaged endothelium, promoting their accumulation and subsequent release at the IRI site."", ""source_pmid"": ""41491215"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.383334+00:00
toxicity,toxicity_endpoint,1402,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,PDA/CD11b modification improves siRNA nanoparticle release and uptake,B,PubMed title,3501,CD11b-modified ROS/pH-responsive nanoparticles co-deliver Dioscin and siRNA to improve cardiac repair after myocardial infarction by reducing neutrophil recruitment.,40977834,PMC12446780,10.1016/j.mtbio.2025.102226,https://pubmed.ncbi.nlm.nih.gov/40977834/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""PDA/CD11b-modified nanoparticle carrying siRNA showed stimulus-triggered release and uptake; abstract support so Grade B."", ""grounding_quote"": ""Nanomaterials were also equipped with polydopamine (PDA) and CD11b to respond to reactive oxygen species/pH in the lesion environment and target neutrophils, respectively. As expected, Dio/siICAM-1@MSN@PDA-CD11b was successfully constructed to realize the rapid release of Dio and siICAM-1 under condition of pH6.4+H2O2. It also exhibited enhanced targeting properties with more intracellular uptake by neutrophils."", ""source_pmid"": ""40977834"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.383334+00:00
toxicity,toxicity_endpoint,1403,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,fluorocarbon/aptamer comodification enhances siRNA delivery,B,PubMed abstract sentence 4,3571,Programmable Comodification of DNA Soccer Framework with Fluorocarbon and Aptamer for Efficient siRNA Delivery.,40747059,PMC12308423,10.1021/jacsau.5c00474,https://pubmed.ncbi.nlm.nih.gov/40747059/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Fluorocarbon/aptamer comodified DNA framework improved siRNA internalization, release and silencing; abstract support so Grade B."", ""grounding_quote"": ""Systematic optimization revealed that a surface modification ratio of 3:1 (fluorocarbon to aptamer) among the 90 available sites yielded synergistic improvements in internalization and cytosolic release, significantly enhancing siRNA-mediated gene silencing."", ""source_pmid"": ""40747059"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.384332+00:00
toxicity,toxicity_endpoint,1404,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,cholesterol-siRNA conjugate liver macrophage delivery,B,PubMed abstract sentence 7,4047,Cholesterol-Conjugated siRNA Silencing Tnf for the Treatment of Liver Macrophage-Mediated Acute Inflammation in Nonalcoholic Fatty Liver Disease.,36318487,,10.1089/nat.2022.0038,https://pubmed.ncbi.nlm.nih.gov/36318487/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Cholesterol-siRNA conjugate showed delivery and anti-inflammatory activity; abstract support so Grade B."", ""grounding_quote"": ""In this study, we characterize a simple cholesterol-short-interfering RNA (siRNA) conjugate system targeting Tnf mRNA in liver macrophages for the treatment of NAFLD. First, we observed delivery and anti-inflammatory activity in an acute liver inflammation model."", ""source_pmid"": ""36318487"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.384332+00:00
toxicity,toxicity_endpoint,1405,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,chemically modified siRNA allele-specific silencing,B,PubMed abstract sentence 2,4061,Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.,36192390,PMC9530163,10.1038/s41467-022-33061-x,https://pubmed.ncbi.nlm.nih.gov/36192390/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Chemically modified siRNAs achieved allele-specific mutant huntingtin lowering; abstract support so Grade B."", ""grounding_quote"": ""Chemically modified siRNAs distinguish between mutant and normal huntingtin based on a single nucleotide difference and lower mutant huntingtin specifically in patient derived cells"", ""source_pmid"": ""36192390"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.385331+00:00
toxicity,toxicity_endpoint,1406,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,2'-O-methyl/5' stabilization improves placental siRNA,B,PubMed abstract sentence 4,4069,Chemical optimization of siRNA for safe and efficient silencing of placental sFLT1.,35847173,PMC9263991,10.1016/j.omtn.2022.06.009,https://pubmed.ncbi.nlm.nih.gov/35847173/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Specific siRNA chemical optimization improved placental accumulation, silencing and safety; abstract support so Grade B."", ""grounding_quote"": ""Here, we systematically evaluate these parameters and demonstrate that increasing 2′-O-methyl modifications and 5′ chemical stabilization and using sequence-specific duplex asymmetry and a phosphocholine-docosanoic acid conjugate enhance placental accumulation, silencing efficiency and safety of sFLT1-targeting siRNAs."", ""source_pmid"": ""35847173"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.385331+00:00
toxicity,toxicity_endpoint,1407,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,Pip6a conjugation enhances PMO muscle delivery,B,PubMed abstract sentence 4,4212,Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice.,31479430,PMC6819114,10.1172/JCI128205,https://pubmed.ncbi.nlm.nih.gov/31479430/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Pip6a-PMO conjugation enhanced ASO muscle delivery versus unconjugated PMO; abstract support so Grade B."", ""grounding_quote"": ""Pip6a-conjugated morpholino phosphorodiamidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following systemic administration in comparison with unconjugated PMO and other ASO strategies."", ""source_pmid"": ""31479430"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.386838+00:00
toxicity,toxicity_endpoint,1408,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,sgc8 aptamer conjugation improves siRNA nanoparticle targeting,B,PubMed abstract sentence 5,12442,Aptamer sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia.,39583320,PMC11585994,10.2147/IJN.S477597,https://pubmed.ncbi.nlm.nih.gov/39583320/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""sgc8-conjugated siBCL11B nanoparticle selectively targeted cells and inhibited viability; abstract support so Grade B."", ""grounding_quote"": ""We demonstrate that sgc8-conjugated siBCL11B nanoparticles selectively and efficiently target BCL11B-overexpressing T-ALL cells, significantly inhibiting cell viability and promoting apoptosis"", ""source_pmid"": ""39583320"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.394845+00:00
toxicity,toxicity_endpoint,1409,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,fully modified siRNA improves tissue retention,B,PubMed abstract sentence 4,12636,Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo.,29432571,PMC5861422,10.1093/nar/gky037,https://pubmed.ncbi.nlm.nih.gov/29432571/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Fully chemically modified siRNAs showed greater tissue retention and productive silencing; abstract support so Grade B."", ""grounding_quote"": ""We show that fully modified siRNAs are retained at 100x greater levels in various tissues, independently of the nature of the conjugate or siRNA sequence, and support productive mRNA silencing."", ""source_pmid"": ""29432571"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.403740+00:00
toxicity,toxicity_endpoint,1410,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,chemistry,5'-vinylphosphonate improves siRNA accumulation/silencing,B,PubMed abstract sentence 4,12652,5΄-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo.,28591791,PMC5570069,10.1093/nar/gkx507,https://pubmed.ncbi.nlm.nih.gov/28591791/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""5'-vinylphosphonate modification improved conjugated siRNA tissue accumulation and silencing duration; abstract support so Grade B."", ""grounding_quote"": ""Specifically, 5΄-vinylphosphonate (i) increases siRNA accumulation in tissues, (ii) extends duration of silencing in multiple organs and (iii) protects siRNAs from 5΄-to-3΄ exonucleases."", ""source_pmid"": ""28591791"", ""candidate_domain"": ""chemistry""}",2026-06-07T21:51:24.410255+00:00
toxicity,toxicity_endpoint,1411,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,TfR antibody-ASO brain transcytosis delivery,C,PubMed abstract sentence 2,1080,Improved targeted delivery of antisense oligonucleotide with an antibody mask.,41166443,PMC12574672,10.1093/nar/gkaf487,https://pubmed.ncbi.nlm.nih.gov/41166443/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""TfR antibody-ASO conjugates show brain delivery via transcytosis; weak abstract support so Grade C."", ""grounding_quote"": ""transferrin receptor (TfR)-targeting antibody–ASO conjugates have shown promise for brain delivery of ASOs via transcytosis in preclinical studies."", ""source_pmid"": ""41166443"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.410255+00:00
toxicity,toxicity_endpoint,1412,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,PEG-(GK)10 ASO polyplex sentinel lymph node delivery,C,PubMed abstract sentence 3,1246,Structurally Dynamic Polyplexes Enhance Sentinel Lymph Node Delivery of Antisense Oligonucleotides to Inhibit Breast Cancer Recurrence and Metastasis.,40540297,,10.1021/jacs.5c04234,https://pubmed.ncbi.nlm.nih.gov/40540297/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Dynamic ASO polyplex enriched ASO in sentinel lymph nodes and improved delivery; abstract support so Grade C."", ""grounding_quote"": ""Here, we demonstrated a molecular approach to engineering a dynamic polyplex, predominantly comprising two poly(ethylene glycol)-(glycine-lysine)10 [PEG-(GK)10] per antisense oligonucleotide (ASO) based on charge neutralization at a minimum molecular ratio, that can enhance SLN functional delivery of ASOs for replenishing immunity against breast cancer recurrence and metastasis. Using a murine breast cancer model, we successfully enriched the ASO distribution in the SLN while limiting off-target organ distribution by tuning the size of the PEG (3-80 kDa)."", ""source_pmid"": ""40540297"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.411256+00:00
toxicity,toxicity_endpoint,1413,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,PNMVA lipid carrier siRNA uptake/endosomal escape,C,PubMed abstract sentence 2,1926,Poly(N-methyl-N-vinylacetamide): A Strong Alternative to PEG for Lipid-Based Nanocarriers Delivering siRNA.,37994483,,10.1002/adhm.202302712,https://pubmed.ncbi.nlm.nih.gov/37994483/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""PNMVA lipid carrier preserved siRNA lipoplex uptake and endosomal escape; abstract support so Grade C."", ""grounding_quote"": ""This work highlights the great potential of amphiphilic poly(N-methyl-N-vinylacetamide) (PNMVA) derivatives as alternatives to lipid-PEG for siRNA delivery. PNMVA compounds with different degrees of polymerization and hydrophobic segments, are synthesized. Among them, DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine)-PNMVA efficiently integrates into lipoplexes and LNP membranes and prevents protein corona formation around these lipid carriers, exhibiting stealth properties comparable to DSPE-PEG. However, unlike DSPE-PEG, DSPE-PNMVA24 shows no adverse impact on lipoplexes cell uptake and endosomal escape."", ""source_pmid"": ""37994483"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.411256+00:00
toxicity,toxicity_endpoint,1414,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,aptamer-mediated tumor accumulation of cisplatin conjugate,C,PubMed abstract sentence 4,2204,Nucleic Acid Aptamers Increase the Anticancer Efficiency and Reduce the Toxicity of Cisplatin-Arabinogalactan Conjugates In Vivo.,35921069,,10.1089/nat.2022.0024,https://pubmed.ncbi.nlm.nih.gov/35921069/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Nucleic-acid aptamer conjugate improved tumor accumulation and targeted delivery; abstract support so Grade C."", ""grounding_quote"": ""Cisplatin-arabinogalactan-aptamer (Cis-AG-Ap) conjugate was synthesized based on Cis-dichlorodiammineplatinum, Siberian larch arabinogalactan, and aptamer AS-42 specific to heat-shock proteins (HSP) 71 kDa (Hspa8) and HSP 90-beta (Hsp90ab1). The antitumor effect was estimated using ascites and metastatic Ehrlich tumor models. Cis-AG-Ap toxicity was assessed by blood biochemistry on healthy mice. Here, we demonstrated enhanced anticancer activity of Cis-AG-Ap and its specific accumulation in tumor foci. It was shown that targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity."", ""source_pmid"": ""35921069"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.412255+00:00
toxicity,toxicity_endpoint,1415,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,PLGA/GelMA hydrogel siRNA cytoplasmic delivery,C,PubMed abstract sentence 4,3276,A smart nanocomposite bioactive ink for controlled siRNA delivery in calvarial mesenchymal stromal cells as a minimally invasive treatment for craniosynostosis.,41647289,PMC12869795,10.1093/rb/rbaf115,https://pubmed.ncbi.nlm.nih.gov/41647289/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Hydrogel/PLGA platform delivered therapeutic FGFR2 siRNA with cytoplasmic delivery; abstract support so Grade C."", ""grounding_quote"": ""PLGA NPs demonstrated high siRNA encapsulation efficiency, efficient cytoplasmic delivery"", ""source_pmid"": ""41647289"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.413265+00:00
toxicity,toxicity_endpoint,1416,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,scFv macrophage-membrane liposome siRNA uptake,C,PubMed title,3529,Biomimetic nanoparticles coated with ScFv-modified macrophage membranes for siRNA delivery to relieve brain metastases of lung cancer.,40898177,PMC12406594,10.1186/s12896-025-01000-5,https://pubmed.ncbi.nlm.nih.gov/40898177/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""scFv-modified macrophage-membrane liposomes improved LPCAT1 siRNA uptake and silencing; abstract support so Grade C."", ""grounding_quote"": ""In vitro, scFv-MML@LPCAT1si exhibited superior cellular uptake and silencing of LPCAT1 expression in EGFR-positive PC9 cells"", ""source_pmid"": ""40898177"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.413265+00:00
toxicity,toxicity_endpoint,1417,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,hydrophobically modified peptide lung siRNA delivery,C,PubMed abstract sentence 1,3950,Identification of Potent siRNA Delivery Peptides Using Computer Modeling.,38311577,PMC11005685,10.1002/advs.202308345,https://pubmed.ncbi.nlm.nih.gov/38311577/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Hydrophobically modified peptide delivered siRNA to lung; abstract support so Grade C."", ""grounding_quote"": ""The leading candidate peptide selected from a library containing 12 amino acids showed strong lung‐targeted siRNA delivery capacity after hydrophobic modification."", ""source_pmid"": ""38311577"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.416260+00:00
toxicity,toxicity_endpoint,1418,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,PAMAM dendrimer morpholino cellular delivery,C,PubMed abstract sentence 1,4246,Dendritic nanoconjugates for intracellular delivery of neutral oligonucleotides.,26134311,PMC4598944manuscript-id: NIHMS704679,10.1039/c5nr01665g,https://pubmed.ncbi.nlm.nih.gov/26134311/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""PAMAM-morpholino nanoconjugates enhanced cellular oligonucleotide delivery; abstract support so Grade C."", ""grounding_quote"": ""Conjugation of neutral morpholino oligonucleotides (ONs) with PAMAM dendrimers resulted in neutral, uniform, and ultra-small (~10nm) nanoconjugates. The nanoconjugates dramatically enhanced cellular delivery of the ONs in cancer cells."", ""source_pmid"": ""26134311"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.419781+00:00
toxicity,toxicity_endpoint,1419,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,RGD/KA26 nanoparticle NSUN2 siRNA uptake,C,PubMed abstract sentence 1,4844,Nanocarriers engineering for efficient NSUN2 silencing and immune responsive therapy in metastatic colorectal cancer.,42093739,PMC13141635,10.1016/j.mtbio.2026.103116,https://pubmed.ncbi.nlm.nih.gov/42093739/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""PLA-RGD-KA26 siRNA nanocomplexes enhanced uptake and NSUN2 knockdown; abstract support so Grade C."", ""grounding_quote"": ""The resulting PLA-RGD-KA26-siRNA nanocomplexes (PRR) exhibited uniform nanoscale dimensions, a positive surface charge, and high colloidal stability in aqueous solution. In vitro studies demonstrated significantly enhanced cellular uptake and efficient NSUN2 knockdown across multiple CRC cell lines"", ""source_pmid"": ""42093739"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.422781+00:00
toxicity,toxicity_endpoint,1420,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,SANG tumor RNAi payload delivery,C,PubMed abstract sentence 2,6833,Tumor agnostic drug delivery with dynamic nanohydrogels.,41500988,PMC12780282,10.1038/s41467-025-66788-4,https://pubmed.ncbi.nlm.nih.gov/41500988/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""SANGs accumulated in tumors and delivered RNAi payloads suppressing oncogenes; abstract support so Grade C."", ""grounding_quote"": ""After intravenous injection, SANGs preferentially accumulate and are retained in primary and metastatic loci in four aggressive cancer models in rodents. SANGs deliver multiple RNAi payloads that significantly suppress oncogene expression and sensitize previously resistant tumors while being safe and well tolerated in simulated clinical applications across three species."", ""source_pmid"": ""41500988"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.426285+00:00
toxicity,toxicity_endpoint,1421,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,recNANP conditional RNAi inducer release,C,PubMed abstract sentence 5,8595,Reconfigurable Nucleic Acid Nanoparticles with Therapeutic RNAi Responses to Intracellular Disease Markers.,40852577,PMC12369976manuscript-id: NIHMS2101912,10.1002/adfm.202508122,https://pubmed.ncbi.nlm.nih.gov/40852577/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""recNANPs conditionally released RNAi inducers and prolonged gene silencing; abstract support so Grade C."", ""grounding_quote"": ""The reconfigurable nucleic acid nanoparticles, or recNANPs, recognize overexpressed cancer biomarkers and conditionally release RNAi inducers targeting apoptosis inhibitors in pancreatic cancer cells. RecNANPs are non-immunostimulatory, achieve prolonged gene silencing compared to conventional RNAi inducers"", ""source_pmid"": ""40852577"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.431291+00:00
toxicity,toxicity_endpoint,1422,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,DNA nanohydrogel ASO release after uptake,C,PubMed abstract sentence 1,9651,A pH-Responsive Dendritic-DNA-Based Nanohydrogel for Dual Drug Delivery.,40305283,PMC12024947,10.3390/biom15040537,https://pubmed.ncbi.nlm.nih.gov/40305283/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""DNA nanohydrogel released ASOs after cellular uptake and enhanced cancer-cell inhibition; abstract support so Grade C."", ""grounding_quote"": ""Upon cellular uptake by cancer cells, the nanocarrier disassembled in the acidic tumor microenvironment, releasing DOX for chemotherapy and ASOs via toehold-mediated strand displacement (TMSD) for targeted gene silencing. Cellular studies demonstrated significantly enhanced cancer cell inhibition compared to single-agent treatments, highlighting strong combined effects."", ""source_pmid"": ""40305283"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.435289+00:00
toxicity,toxicity_endpoint,1423,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,hyaluronic acid nanocarrier siGLUT1 tumor delivery,C,PubMed title,9875,Overcoming chemoresistance in acute myeloid leukemia via co-delivery of siGLUT1 and hydroxycamptothecin using hyaluronic acid-conjugated nanocarriers.,40147647,,10.1016/j.ijbiomac.2025.142492,https://pubmed.ncbi.nlm.nih.gov/40147647/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""HA-conjugated nanocarrier delivered GLUT1 siRNA to tumor sites and improved uptake; abstract support so Grade C."", ""grounding_quote"": ""In this study, we developed a biocompatible co-delivery system that incorporates hydroxycamptothecin (HCPT) and glucose transporter 1 (GLUT1) small interfering RNA (siRNA). HCPT was loaded onto gold nanoparticles through crystallization, ensuring drug stability and safety. The branched configuration of self-branched chitosan contributed to improved gene delivery efficiency. The hyaluronic acid-conjugated nanocarrier specifically targeted CD44 receptors expressed on AML cells, while the pH-sensitive properties of self-branched chitosan promoted localized drug and gene release. This system effectively delivered the therapeutic agents to tumor sites, improving cellular uptake"", ""source_pmid"": ""40147647"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.438798+00:00
toxicity,toxicity_endpoint,1424,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,mannosylated peptidyl lipid siG12S tumor delivery,C,PubMed abstract sentence 1,9951,A Mannosylated peptidyl lipid CManDA doped into cytidinyl/cationic lipids efficiently delivers siG12Ss to lung cancer in vivo.,40073943,,10.1016/j.jconrel.2025.113624,https://pubmed.ncbi.nlm.nih.gov/40073943/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""CManDA/DNCA/CLD lipid system delivered siG12S with tumor targeting and silencing; abstract support so Grade C."", ""grounding_quote"": ""Here, we designed and synthesized a Gemini-type mannosylated peptidyl lipid called CManDA(M), which, in combination with the cytidinyl lipid DNCA(D) and the peptidyl lipid CLD(C) (D/50C/50M), could transfect siRNA (siG12S) into A549 cells to target and silence the KRASG12S gene. The fluorescence intensity in the tumor area of the D/50C/50M/Cy5.5-siG12S group increased by approximately 2.5 times. Furthermore, full 2'-F/2'-OMe-modified siG12Ss could also be transfected by D/50C/50M into cells, resulting in target gene silencing. The tumor weight in the D/50C/50M/M3 group (1.5 mg/kg, i.v.) was reduced by 50 % after administration in a mouse axillary tumor (A549) model, whereas the tumor bioluminescence intensity was only approximately 30 % of that in the blank group in a mouse orthotopic lung cancer model and showed no significant toxicity."", ""source_pmid"": ""40073943"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.442306+00:00
toxicity,toxicity_endpoint,1425,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,lysine-modified chitosan siRNA uptake,C,PubMed abstract sentence 1,12104,"A novel, non-toxic chitosan modified with lysine to enhance buffer capacity for siRNA delivery.",39348656,,,https://pubmed.ncbi.nlm.nih.gov/39348656/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Lysine-modified chitosan bound siRNA and showed uptake/transfection efficiency; abstract support so Grade C."", ""grounding_quote"": ""The results showed that LGCS could effectively bind to siRNA and form a complex with a hydrated diameter of about 97.2 ± 1.3 nm. Furthermore, cytotoxicity assays conducted on RSC96 cells demonstrated that LGCS exhibited lower toxicity compared to linear polyethyleneimine (PEI) 25k. In vitro, cellular uptake assays also revealed that LGCS displayed excellent transfection efficiency."", ""source_pmid"": ""39348656"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.447501+00:00
toxicity,toxicity_endpoint,1426,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,modified PEI nanoparticle siRNA transfection efficacy,C,PubMed title,12538,Analysis of polymeric nanoparticle properties for siRNA/DNA delivery in a tumor xenograft tissue slice air-liquid interface model.,36541426,,10.1002/biot.202200415,https://pubmed.ncbi.nlm.nih.gov/36541426/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""3D tissue-slice testing observed siRNA nanoparticle transfection efficacy differences; abstract support so Grade C."", ""grounding_quote"": ""When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture."", ""source_pmid"": ""36541426"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.456502+00:00
toxicity,toxicity_endpoint,1427,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,ZNF416 siRNA liposome fibrotic lung targeting,C,PubMed abstract sentence 8,12545,Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.,36371191,PMC9652794,10.1186/s12967-022-03740-w,https://pubmed.ncbi.nlm.nih.gov/36371191/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""ZNF416 siRNA liposomes passively targeted fibrotic lung after tail-vein delivery; abstract support so Grade C."", ""grounding_quote"": ""Besides, ZNF416 siRNA-loaded liposome delivery by tail-vein could passively target the fibrotic area in the lung"", ""source_pmid"": ""36371191"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.465490+00:00
toxicity,toxicity_endpoint,1428,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,pH-responsive NP siRNA-prodrug tumor release,C,PubMed abstract sentence 1,12601,Stimuli-Responsive Polymer-Prodrug Hybrid Nanoplatform for Multistage siRNA Delivery and Combination Cancer Therapy.,31381852,,10.1021/acs.nanolett.9b01660,https://pubmed.ncbi.nlm.nih.gov/31381852/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""pH-responsive polymer-prodrug NPs accumulated in tumors and released siRNA-prodrug complexes; abstract support so Grade C."", ""grounding_quote"": ""After intravenous administration, the long-circulating NPs accumulate in tumor tissues and then rapidly release the siRNA-prodrug complexes via TME pH-mediated NP disassociation for subsequent tissue penetration and cytosolic transport."", ""source_pmid"": ""31381852"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.470517+00:00
toxicity,toxicity_endpoint,1429,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,cysteamine gold nanoparticle siRNA delivery,C,PubMed abstract sentence 7,13711,Cysteamine functionalized gold nanoparticles exhibit high efficiency delivery of genetic materials in embryonic stem cells majorly via clathrin mediated endocytosis.,39521158,,10.1016/j.ijpharm.2024.124928,https://pubmed.ncbi.nlm.nih.gov/39521158/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Cysteamine gold nanoparticles delivered siRNA with target silencing; abstract support so Grade C."", ""grounding_quote"": ""We also observed that about 70 % transient silencing of the target gene was achieved with only 25 nM siRNA delivered by our nano-vehicle."", ""source_pmid"": ""39521158"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.476520+00:00
toxicity,toxicity_endpoint,1430,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,delivery,magnetic hyperthermia siRNA transfection,C,PubMed abstract sentence 2,13877,Membrane-localized magnetic hyperthermia promotes intracellular delivery of cell-impermeant probes.,39052238,,10.1039/d4nr01955e,https://pubmed.ncbi.nlm.nih.gov/39052238/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Magnetic hyperthermia enabled siRNA transfection with lower toxicity; abstract support so Grade C."", ""grounding_quote"": ""Finally, we demonstrate the utility of this approach for the transfection of cells with a small interference RNA (siRNA), revealing a similar efficacy to a standard transfection method based on the use of cationic lipid-based reagents (such as Lipofectamine), but with lower cell toxicity."", ""source_pmid"": ""39052238"", ""candidate_domain"": ""delivery""}",2026-06-07T21:51:24.482725+00:00
toxicity,toxicity_endpoint,1431,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,hepatic innate immune cytokine induction,C,source title,4262,Chemical modifications on siRNAs avoid Toll-like-receptor-mediated activation of the hepatic immune system in vivo and in vitro.,24065781,,10.1093/intimm/dxt040,https://pubmed.ncbi.nlm.nih.gov/24065781/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Unmodified siRNA induced hepatic innate immune cytokines, while chemically modified siRNA did not; abstract-only generic siRNAs so Grade C."", ""grounding_quote"": ""Unmodified GAL siRNA transiently induced the expression of TNF-α, IL-6, IL-10, IFN-β and IFN-sensitive gene 15 in vivo, whereas a formulation of 2'-O-methylated-LUC siRNA had no such effects."", ""source_pmid"": ""24065781"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.230374+00:00
toxicity,toxicity_endpoint,1432,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,general in vivo safety profile,C,PubMed abstract sentence 6,1900,Imidazolyl Lipids Enhanced LNP Endosomal Escape for Ferroptosis RNAi Treatment of Cancer.,38829038,,10.1002/smll.202402362,https://pubmed.ncbi.nlm.nih.gov/38829038/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Fc-siRNA LNP formulation reports an observed in vivo safety profile, but endpoint detail is generic so Grade C."", ""grounding_quote"": ""Moreover, Fc-siRNA@O-LNPs encapsulated with ferrocene (Fc) and SLC7A11/Nrf2-targeted siRNA is formulated. The outcomes demonstrate optimal safety profiles and a significant anti-tumor effect by inducing long-lasting and efficient ferroptosis through a synergistic action in vivo."", ""source_pmid"": ""38829038"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.231373+00:00
toxicity,toxicity_endpoint,1433,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,mouse nontoxicity,C,PubMed abstract sentence 1,2002,Pronounced therapeutic potential of oligonucleotides fixed on inorganic nanoparticles against highly pathogenic H5N1 influenza A virus in vivo.,33753212,,10.1016/j.ejpb.2021.03.006,https://pubmed.ncbi.nlm.nih.gov/33753212/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Oligonucleotide nanocomposites were administered in mice and reported as nontoxic under the tested conditions; generic ODN/ODNm support so Grade C."", ""grounding_quote"": ""new delivery system consisting of biocompatible low-toxic titanium dioxide nanoparticles and immobilized polylysine-containing oligonucleotides with the native (ODN) and partially modified (ODNm) internucleotide bonds. Intraperitoneal injection of the TiO2•PL-ODN nanocomposite provided 65-70% survival of mice, while intraperitoneal or oral administration of TiO2•PL-ODNm was somewhat more efficient (~80% survival). The virus titer in the lung was reduced by two-three orders of magnitude. The nanocomposites are nontoxic to mice under the used conditions."", ""source_pmid"": ""33753212"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.231373+00:00
toxicity,toxicity_endpoint,1434,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,no adverse effects,C,PubMed abstract sentence 5,2009,Development of Prodrug Type Circular siRNA for In Vivo Knockdown by Systemic Administration.,33016851,,10.1089/nat.2020.0894,https://pubmed.ncbi.nlm.nih.gov/33016851/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Systemically administered circular siRNA showed in vivo activity without adverse effects; generic platform support so Grade C."", ""grounding_quote"": ""after systemic administration to mice, circular siRNA showed prolonged circulation and improved knockdown activity in the liver, kidney, and muscle, without causing adverse effects."", ""source_pmid"": ""33016851"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.231373+00:00
toxicity,toxicity_endpoint,1435,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,reduced side effects,B,PubMed abstract sentence 1,2015,A selective Aurora-A 5'-UTR siRNA inhibits tumor growth and metastasis.,31875524,,10.1016/j.canlet.2019.12.031,https://pubmed.ncbi.nlm.nih.gov/31875524/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Named LNA-siRNA-2 had an observed improved safety/reduced side-effect result in xenograft models; abstract-only support so Grade B."", ""grounding_quote"": ""a selective siRNA, siRNA-2, which targets Aurora-A mRNA exon 2, was designed to translationally inhibit the expression of Aurora-A in cancer cells but not normal cells; locked nucleic acid (LNA)-modified siRNA-2 showed improved efficacy in inhibiting Aurora-A mRNA translation and tumor growth. Xenograft animal models combined with noninvasion in vivo imaging system (IVIS) analysis further confirmed the anticancer effect of LNA-siRNA-2 with improved efficiency and safety and reduced side effects."", ""source_pmid"": ""31875524"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.231373+00:00
toxicity,toxicity_endpoint,1436,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,cell cytotoxicity absence,C,PubMed abstract sentence 13,2644,Evaluation of the effects of storage conditions on spray-dried siRNA-LNPs before and after subsequent drying.,37956785,,10.1016/j.ejpb.2023.11.007,https://pubmed.ncbi.nlm.nih.gov/37956785/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""RNA-loaded LNP formulation retained activity and lacked cytotoxic effects in a safety-sense cell assay; generic delivery platform so Grade C."", ""grounding_quote"": ""Spray-dried LNPs maintained bioactivity resulting in > 95 % protein downregulation and confirming the lack of cytotoxic effects in a lung adenocarcinoma cell line. Furthermore, the spray-dried and subsequently dried LNPs stored for 3 months at 4 °C and 25 °C achieved up to 50 % gene silencing of the house-keeping gene GAPDH after deposition on the mucus layer of Calu-3 cells. This study confirms the stability of spray-dried and subsequently dried LNPs over at least 90 days at 4 °C and 25 °C emphasizing the potential of dry powder inhalation of RNA-loaded LNPs as a therapy option for pulmonary diseases."", ""source_pmid"": ""37956785"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.231373+00:00
toxicity,toxicity_endpoint,1437,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,adverse events,B,PubMed abstract sentence 3,2652,"A Phase I Study of TRK-250, a Novel siRNA-Based Oligonucleotide, in Patients with Idiopathic Pulmonary Fibrosis.",37738329,,10.1089/jamp.2023.0014,https://pubmed.ncbi.nlm.nih.gov/37738329/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Phase I TRK-250 study reports observed adverse-event findings after inhaled dosing; named clinical oligo and abstract-only support so Grade B."", ""grounding_quote"": ""Purpose: TRK-250 is a novel single-stranded oligonucleotide carrying a human Transforming growth factor-beta 1-targeting siRNA motif tethered by two proline linkers. Nonclinical studies have shown that TRK-250 may have potency to prevent the progression of pulmonary fibrosis. Herein, a phase I study was conducted to investigate the safety and pharmacokinetics (PKs) of TRK-250 in patients with idiopathic pulmonary fibrosis (IPF). Method: In the phase I study, 34 IPF patients were partially randomized to receive a placebo or TRK-250 in 4 single doses of 2, 10, 30, and 60 mg or multiple rising doses of 10, 30, and 60 mg once per week for 4 weeks by oral inhalation. For both the single- and multiple-dose studies, the primary endpoint was safety, and the secondary endpoint was PKs. Result: In all IPF patients who orally inhaled TRK-250, no significant drug-related adverse events (AEs) were observed. The AEs were mild or moderate, except for one severe case with acute exacerbation. One of the more common AEs was coughing. One patient discontinued treatment before the last dose because of coughing."", ""source_pmid"": ""37738329"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.232879+00:00
toxicity,toxicity_endpoint,1438,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,IL-6 and CRP immune activation,B,PubMed abstract sentence 3,2712,Early-Stage Identification and Avoidance of Antisense Oligonucleotides Causing Species-Specific Inflammatory Responses in Human Volunteer Peripheral Blood Mononuclear Cells.,35976085,,10.1089/nat.2022.0033,https://pubmed.ncbi.nlm.nih.gov/35976085/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""ISIS 353512 ASO caused IL-6 and CRP increases and PBMC immune activation linked to TLR signaling; abstract-only named ASO so Grade B."", ""grounding_quote"": ""A human peripheral blood mononuclear cell (PBMC)-based assay was developed to identify antisense oligonucleotide (ASO) with the potential to activate a cellular innate immune response outside of an acceptable level. The development of this assay was initiated when ISIS 353512 targeting the messenger ribonucleic acid for human C-reactive protein (CRP) was tested in a phase I clinical trial, in which healthy human volunteers unexpectedly experienced increases in interleukin-6 (IL-6) and CRP. This level of immune stimulation was not anticipated following rodent and nonhuman primate safety studies in which no evidence of exaggerated proinflammatory effects were observed. The IL-6 increase induced by ISIS 353512 was caused by activation of B cells. The IL-6 induction was inhibited by chloroquine pretreatment of PBMCs and the nature of ASOs suggested that the response is mediated by a Toll-like receptor (TLR), in all likelihood TLR9."", ""source_pmid"": ""35976085"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.232879+00:00
toxicity,toxicity_endpoint,1439,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,adverse drug reactions,B,PubMed abstract sentence 4,2789,Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy.,29669851,,10.1126/scitranslmed.aan0713,https://pubmed.ncbi.nlm.nih.gov/29669851/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Clinical NS-065/NCNP-01 morpholino ASO dosing reports no severe adverse drug reactions or discontinuations; abstract-only support so Grade B."", ""grounding_quote"": ""We conducted a phase 1, open-label, dose-escalation clinical trial to determine the safety, pharmacokinetics, and activity of NS-065/NCNP-01, a morpholino ASO that enables skipping of exon 53. Ten patients with DMD (6 to 16 years old), carrying mutations in the dystrophin gene whose reading frame would be restored by exon 53 skipping, were administered NS-065/NCNP-01 at doses of 1.25, 5, or 20 mg/kg weekly for 12 weeks. The primary endpoint was safety; the secondary endpoints were pharmacokinetics and successful exon skipping. No severe adverse drug reactions were observed, and no treatment discontinuation occurred."", ""source_pmid"": ""29669851"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.232879+00:00
toxicity,toxicity_endpoint,1440,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,clinical tolerability,B,PubMed abstract sentence 6,2804,"Suppressing transthyretin production in mice, monkeys and humans using 2nd-Generation antisense oligonucleotides.",27355239,,10.1080/13506129.2016.1191458,https://pubmed.ncbi.nlm.nih.gov/27355239/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""IONIS-TTRRx ASO was administered in healthy volunteers and reported well tolerated without remarkable safety issues; abstract-only support so Grade B."", ""grounding_quote"": ""IONIS-TTRRx (ISIS 420915) is a 2nd-Generation 2'-O-(2-methoxyethyl) modified \""2'-MOE\"" antisense oligonucleotide (ASO) that targets the TTR RNA transcript and reduces the levels of the TTR transcript through an RNaseH1 mechanism of action, leading to reductions in both mutant and wild-type TTR protein. The activity of IONIS-TTRRx to decrease TTR protein levels was studied in transgenic mice bearing the Ile84Ser human TTR mutant, in cynomolgus monkeys and in healthy human volunteers. Robust (>80%) reductions of plasma TTR protein were obtained in all three species treated with IONIS-TTRRx, which in mice and monkeys was associated with substantial reductions in hepatic TTR RNA levels. These effects were dose-dependent and lasted for weeks post-dosing. In a Phase 1 healthy volunteer study, treatment with IONIS-TTRRx for four weeks was well tolerated without any remarkable safety issues."", ""source_pmid"": ""27355239"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.232879+00:00
toxicity,toxicity_endpoint,1441,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,renal tubular degeneration and glomerulopathy,B,PubMed abstract sentence 1,2825,Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.,24292388,,10.1177/0192623313505781,https://pubmed.ncbi.nlm.nih.gov/24292388/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Chronic drisapersen AON administration produced renal tubular degeneration and glomerulopathy; abstract-only named AON so Grade B."", ""grounding_quote"": ""Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics."", ""source_pmid"": ""24292388"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.232879+00:00
toxicity,toxicity_endpoint,1442,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,genotoxicity/mutagenesis,C,PubMed abstract sentence 3,2831,Mutagenesis by an antisense oligonucleotide and its degradation product.,22872057,,10.1093/toxsci/kfs247,https://pubmed.ncbi.nlm.nih.gov/22872057/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""A biologically active antisense molecule induced sequence-specific genomic mutation in cells; unnamed/generic ASO support so Grade C."", ""grounding_quote"": ""Treating human lymphoblastoid cells with a biologically active antisense molecule induced sequence-specific mutation within genomic DNA over fourfold"", ""source_pmid"": ""22872057"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.233886+00:00
toxicity,toxicity_endpoint,1443,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,absence of adverse systemic effects,B,PubMed abstract sentence 4,3865,Novel injectable polypeptide nanoparticle encapsulated siRNA targeting TGF-β1 and COX-2 for localized fat reduction I: Preclinical in vitro and animal models.,39166716,,10.1111/jocd.16535,https://pubmed.ncbi.nlm.nih.gov/39166716/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""STP705 HKP-siRNA nanoparticle showed localized activity without adverse systemic effects in preclinical models; abstract-only support so Grade B."", ""grounding_quote"": ""RESULTS: STP705 effectively reduced the expression of TGF-β1 and COX-2, with a notable decrease in adipocyte volume and lipid content without adverse systemic effects. In DIO mice, the HKP-siRNA complex demonstrated precise localization to injected adipose tissue, maintaining significant gene silencing, and detectable levels of siRNA for up to 14 days post-administration."", ""source_pmid"": ""39166716"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.235400+00:00
toxicity,toxicity_endpoint,1444,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,reduced adverse reactions,C,PubMed abstract sentence 2,3922,Construction of aptamer-siRNA chimera and glutamine modified carboxymethyl-β-cyclodextrin nanoparticles for the combination therapy against lung squamous cell carcinoma.,38554525,,10.1016/j.biopha.2024.116506,https://pubmed.ncbi.nlm.nih.gov/38554525/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""Aptamer-siRNA chimera nanoparticle therapy reports reduced adverse reactions in animal experiments, but support is generic and combo-product confounded so Grade C."", ""grounding_quote"": ""Here, we constructed an AS1411 aptamer-programmed cell death ligand-1 (PD-L1) siRNA chimera/polyethylenimine/glutamine/β-cyclodextrin/doxorubicin (Chimera/ PEI/Gln/β-CD/DOX) nanoparticle for the combination therapy (chemotherapy combined with immunotherapy). Scanning electron microscopy showed that PEI/Gln/β-CD/DOX nanoparticle was conical, with a diameter of about 250-500 nm. AS1411 aptamer-PD-L1 siRNA chimera can effectively bind NSCLC cells and inhibit PD-L1 expression, further activating T cells and CD8+T cells. Glutamine modification effectively promoted the doxorubicin uptake by cancer cells and induced their apoptosis. Animal experiments showed that our nanoparticles effectively treated the transplanted tumor, and the adverse reactions were reduced."", ""source_pmid"": ""38554525"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.235400+00:00
toxicity,toxicity_endpoint,1445,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,ALT elevations,B,PubMed abstract sentence 4,4000,Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials.,37290591,,10.1016/j.jhep.2023.05.023,https://pubmed.ncbi.nlm.nih.gov/37290591/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""RNAi therapeutics VIR-2218 and ALN-HBV are directly compared for ALT elevations in mice and healthy volunteers; abstract-only named therapeutics so Grade B."", ""grounding_quote"": ""ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts. METHODS: We report on: i) the safety of single doses of VIR-2218 (modified from ALN-HBV by enhanced stabilization chemistry plus technology to reduce off-target, seed-mediated binding while maintaining on-target antiviral activity) and ALN-HBV in humanized mice; ii) a cross-study comparison of the safety of single doses of VIR-2218 and ALN-HBV in healthy human volunteers (n = 24 and n = 49, respectively); and iii) the antiviral activity of two doses of 20, 50, 100, 200 mg of VIR-2218 (total n = 24) vs. placebo (n = 8), given 4 weeks apart, in participants with cHBV infection. RESULTS: In humanized mice, alanine aminotransferase (ALT) levels were markedly lower following administration of VIR-2218 compared with ALN-HBV. In healthy volunteers, post-treatment ALT elevations occurred in 28% of participants receiving ALN-HBV compared with none in those receiving VIR-2218."", ""source_pmid"": ""37290591"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.235400+00:00
toxicity,toxicity_endpoint,1446,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,transaminase increases,B,PubMed abstract sentence 1,4216,Antisense Inhibition of Glucagon Receptor by IONIS-GCGR(Rx) Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy.,30765435,,10.2337/dc18-1343,https://pubmed.ncbi.nlm.nih.gov/30765435/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""IONIS-GCGRRx is an antisense oligo administered in phase 2 studies and dose-dependent liver transaminase increases were observed."", ""grounding_quote"": ""Dose-dependent increases in transaminases were observed with IONIS-GCGRRx, which were attenuated at lower doses and remained mostly within the normal reference range at the 50-mg dose."", ""source_pmid"": ""30765435"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.236908+00:00
toxicity,toxicity_endpoint,1447,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,infusion reactions adverse events,B,PubMed abstract sentence 13,4227,"A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer.",29250742,,10.1007/s10637-017-0553-x,https://pubmed.ncbi.nlm.nih.gov/29250742/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""Apatorsen-treated patients had infusion reactions reported as the most common adverse event."", ""grounding_quote"": ""Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients."", ""source_pmid"": ""29250742"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.236908+00:00
toxicity,toxicity_endpoint,1448,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,adverse events/tolerability,B,PubMed abstract sentence 10,10468,Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B.,39214467,,10.1016/j.jhep.2024.08.010,https://pubmed.ncbi.nlm.nih.gov/39214467/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""Bepirovirsen sequential therapy reports comparable adverse-event proportions and is described as tolerable."", ""grounding_quote"": ""The proportions of participants with adverse events and treatment-related adverse events in both treatment windows were similar between treatment arms. CONCLUSIONS: Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable"", ""source_pmid"": ""39214467"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.242096+00:00
toxicity,toxicity_endpoint,1449,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,minor toxic side effects,C,PubMed abstract sentence 11,10550,Synergistic Therapy of Metastatic Breast Cancers by Biomimetic Chemotherapeutic Drug-Gene Nanoparticles.,39657238,,10.1021/acsami.4c13535,https://pubmed.ncbi.nlm.nih.gov/39657238/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""TPT-ASOVEGF@MM oligo-containing nanodrug showed antimetastatic activity in mice with minor toxic side effects; toxicity detail is generic so Grade C."", ""grounding_quote"": ""In MBC mouse models, the in vivo inhibition rate of TPT-ASOVEGF@MM NPs for lung metastasis was 89.5%, with minor toxic side effects and the least number of metastatic nodules in the lungs."", ""source_pmid"": ""39657238"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.245388+00:00
toxicity,toxicity_endpoint,1450,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,pulmonary surfactant biophysical function,C,PubMed abstract sentence 1,10623,Effect of lipid-polymer hybrid nanoparticles on the biophysical function and lateral structure of pulmonary surfactant: Mechanistic in vitro studies.,39491068,,10.1016/j.jcis.2023.10.036,https://pubmed.ncbi.nlm.nih.gov/39491068/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""siRNA-loaded lipid-polymer nanoparticles for lung inflammation altered pulmonary surfactant function/structure in vitro, a safety-relevant endpoint."", ""grounding_quote"": ""Here, we investigated the effect of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs), which are designed for treatment of lung inflammation, on the physiological function of PS. By using biophysical in vitro methods we show that siRNA-loaded LPNs affect the biophysical function and lateral structure of PS."", ""source_pmid"": ""39491068"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.248910+00:00
toxicity,toxicity_endpoint,1451,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,safety profile/minimal off-target effects,C,PubMed abstract sentence 6,10686,Therapeutic Suppression of Atherosclerotic Burden and Vulnerability via Dll4 Inhibition in Plaque Macrophages Using Dual-Targeted Liposomes.,39392531,,10.1021/acsabm.4c00923,https://pubmed.ncbi.nlm.nih.gov/39392531/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""Dll4-targeting siRNA liposomal system was evaluated for safety with favorable outcomes and minimal off-target effects; toxicity support is generic so Grade C."", ""grounding_quote"": ""By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution."", ""source_pmid"": ""39392531"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.253423+00:00
toxicity,toxicity_endpoint,1452,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,cytokine release/immunostimulation,B,PubMed abstract sentence 1,10749,"Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic.",39306863,,10.1021/acsinfecdis.4c00514,https://pubmed.ncbi.nlm.nih.gov/39306863/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""Imdusiran is an siRNA therapeutic and did not stimulate cytokine release in healthy donor whole blood."", ""grounding_quote"": ""Imdusiran did not intrinsically stimulate cytokine release in healthy donor human whole blood, supportive of its mechanism of action"", ""source_pmid"": ""39306863"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.257446+00:00
toxicity,toxicity_endpoint,1453,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,biosafety,C,PubMed abstract sentence 8,11005,Hepatocyte Growth Factor DNA Aptamer for Prevention of Postoperative Peritoneal Adhesion via Enhancement of Fibrinolysis and Inhibition of Mesothelial Mesenchymal Transition.,38963794,,10.1021/acsabm.4c00507,https://pubmed.ncbi.nlm.nih.gov/38963794/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ql,"{""reason"": ""HGF DNA aptamer is the therapeutic oligo under study and the abstract reports biosafety, but endpoint detail is generic so Grade C."", ""grounding_quote"": ""Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings."", ""source_pmid"": ""38963794"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.261447+00:00
toxicity,toxicity_endpoint,1454,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,hemolysis/no toxic manifestations,C,PubMed abstract sentence 7,11219,H-ras-targeted genetic therapy remarkably surpassed docetaxel treatment in inhibiting chemically induced hepatic tumors in rats.,38697280,,10.1016/j.lfs.2024.122680,https://pubmed.ncbi.nlm.nih.gov/38697280/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Therapeutic PS-ASO had low hemolysis and no toxic manifestations in normal rats; abstract-only generic ASO support so Grade C."", ""grounding_quote"": ""PS-ASO showed low in vitro hemolysis (<3 %), and had a sustained PS-ASO blood residence time in vivo compared to DTX, with a time-dependent hepatic uptake. It showed no toxic manifestations in normal rats."", ""source_pmid"": ""38697280"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.265474+00:00
toxicity,toxicity_endpoint,1455,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,minimal side effects,B,PubMed abstract sentence 4,11250,[SOD1 gene therapy delays ALS disease progression].,38666665,,,https://pubmed.ncbi.nlm.nih.gov/38666665/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Named tofersen ASO was administered and side effects were reported as minimal; abstract-only named oligo support so Grade B."", ""grounding_quote"": ""the patient received monthly intrathecal treatment with tofersen, an antisense oligonucleotide compound that inhibits SOD1 protein expression and hence lowers the synthesis of toxic SOD1 protein species. Side effects have been minimal and mostly attributed to the spinal taps."", ""source_pmid"": ""38666665"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.269017+00:00
toxicity,toxicity_endpoint,1456,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,acceptable safety,B,PubMed abstract sentence 1,11345,"Patisiran, an RNAi therapeutic for hereditary transthyretin-mediated amyloidosis: Sub-analysis in Taiwanese patients from the APOLLO study.",38548524,,10.1016/j.jfma.2024.03.008,https://pubmed.ncbi.nlm.nih.gov/38548524/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Named patisiran RNAi therapeutic trial subanalysis reports acceptable safety; abstract-only named oligo support so Grade B."", ""grounding_quote"": ""BACKGROUND: To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. METHODS: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M. RESULTS: Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], -26.5 points; 95% confidence interval: -45.5, -7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety"", ""source_pmid"": ""38548524"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.274686+00:00
toxicity,toxicity_endpoint,1457,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,safety profile in AS mouse model,C,PubMed abstract sentence 4,11551,Multipathway Regulation for Targeted Atherosclerosis Therapy Using Anti-miR-33-Loaded DNA Origami.,38321605,,10.1021/acsnano.3c10213,https://pubmed.ncbi.nlm.nih.gov/38321605/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Anti-miR-33 DNA origami therapeutic reports a validated safety profile in an AS mouse model; toxicity detail is generic so Grade C."", ""grounding_quote"": ""The antiatherosclerotic efficacy and safety profile of cRGD/ASOtDON, as well as its mechanism of action, were validated in an AS mouse model."", ""source_pmid"": ""38321605"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.278208+00:00
toxicity,toxicity_endpoint,1458,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,non-toxic gene silencing,C,PubMed abstract sentence 8,11863,Impact of the Core Chemistry of Self-Assembled Spherical Nucleic Acids on their In Vitro Fate.,37905978,,10.1002/anie.202315768,https://pubmed.ncbi.nlm.nih.gov/37905978/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Self-assembled spherical nucleic acid gene-silencing therapeutics are reported as non-toxic; generic in vitro support so Grade C."", ""grounding_quote"": ""Disulfide-crosslinked SNAs combine these two properties and result in efficient and non-toxic unaided gene silencing therapeutics."", ""source_pmid"": ""37905978"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.281208+00:00
toxicity,toxicity_endpoint,1459,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,adjacent T-cell sparing,C,PubMed abstract sentence 7,12389,A PD-L1 siRNA-Loaded Boron Nanoparticle for Targeted Cancer Radiotherapy and Immunotherapy.,39955653,,10.1002/adma.202419418,https://pubmed.ncbi.nlm.nih.gov/39955653/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""PD-L1 siRNA nanoparticle treatment reported sparing adjacent T cells, a safety-sense cytotoxicity endpoint; boundary abstract support so Grade C."", ""grounding_quote"": ""Here it develops a 10B-containing polymer that self-assembled with PD-L1 siRNA to form 10B/siPD-L1 nanoparticles for combinational BNCT-immunotherapy. Unlike antibodies, PD-L1 siRNA can inhibit intracellular PD-L1 upregulated by BNCT, activating T-cell immunity while also suppressing DNA repair. This can enhance BNCT-induced DNA damage, promoting immunogenic cell death (ICD) and further amplifying the antitumor immune effect. The results demonstrated that BNCT using 10B/siPD-L1 nanoparticles precisely killed tumor cells while sparing adjacent T cells"", ""source_pmid"": ""39955653"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.284718+00:00
toxicity,toxicity_endpoint,1460,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,promising drug safety in mice,C,PubMed abstract sentence 6,12451,Targeting oncogenic transcriptional factor c-myc by oligonucleotide PROTAC for the treatment of hepatocellular carcinoma.,39447458,,10.1016/j.ejmech.2024.116978,https://pubmed.ncbi.nlm.nih.gov/39447458/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Named oligonucleotide PROTACs MP-16/MP-17 inhibited tumors and exhibited promising drug safety in mice; weak safety detail so Grade C."", ""grounding_quote"": ""Herein, by conjugating VH032 with an optimized DNA sequence that recognized c-Myc complex, we discovered oligonucleotide-based proteolysis targeting chimeras (PROTACs), termed as MP-16 and MP-17, which effectively induced degradation of c-Myc. Mechanically, MP-16 or MP-17 directly interacted with c-Myc complex to form VHL/PROTAC/c-Myc ternary complex, and triggered c-Myc degradation by recruiting ubiquitin-proteasome system, suppressing cell proliferation of HCC cells. In mice model, MP-16 or MP-17 significantly inhibited HCC tumor growth and exhibited promising drug safety."", ""source_pmid"": ""39447458"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.290293+00:00
toxicity,toxicity_endpoint,1461,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,biocompatibility/biosafety in vitro and in vivo,C,PubMed abstract sentence 6,13796,Oral bomb effect nanotherapeutics alleviate ulcerative colitis through coordinated anti-inflammatory and pro-resolving strategies.,39264298,,10.1039/d4bm00843j,https://pubmed.ncbi.nlm.nih.gov/39264298/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""siCD98-loaded nanoparticles had biocompatibility and biosafety evaluated with good in vitro and in vivo results; generic support so Grade C."", ""grounding_quote"": ""The nano-bomb nanoparticles were validated for their ability to load CD98 siRNA (siCD98) and Annexin A1-mimetic peptides (Ac2-26 peptides), as well as release CO2 upon lysosomal escape. Surface modification with hyaluronic acid (HA) was assessed for its capability to target inflammatory tissues and cells. Biocompatibility and biosafety were evaluated through in vitro and in vivo studies. The anti-inflammatory and pro-resolving effects of siCD98@NPs and Ac2-26@NPs, both individually and in combination, were evaluated by measuring ROS production, pro-inflammatory cytokine expression, CD98 gene expression, and macrophage polarization. Results: These nanoparticles could efficiently load siCD98 and Ac2-26 peptides and release CO2 under acidic pH in the endo/lysosome to deliver drugs to the cytoplasm. HA could effectively target the inflammatory tissue and cells, showing good biocompatibility and biosafety both in vitro and in vivo."", ""source_pmid"": ""39264298"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.295812+00:00
toxicity,toxicity_endpoint,1462,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,toxicity,CSF leukocyte count increase,B,PubMed abstract sentence 4,14317,Inflammatory markers in cerebrospinal fluid of paediatric spinal muscular atrophy patients receiving nusinersen treatment.,36525882,,10.1016/j.ejpn.2022.12.003,https://pubmed.ncbi.nlm.nih.gov/36525882/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,gr,"{""reason"": ""Named ASO nusinersen treatment is linked to observed increased CSF leukocyte counts; abstract-only support so Grade B."", ""grounding_quote"": ""The most commonly used therapy for SMA, the antisense oligonucleotide nusinersen, is delivered by repeated intrathecal injections. The long-term safety effects of this procedure, however, have not yet been investigated in detail. We here present case reports of three children with SMA in which routine laboratory investigation revealed increased leukocyte counts in cerebrospinal fluid (CSF) collected during the course of nusinersen treatment."", ""source_pmid"": ""36525882"", ""candidate_domain"": ""toxicity""}",2026-06-07T23:20:28.300319+00:00
offtarget,offtarget_evidence,1,SNA-modified GalNAc-siRNA panel from PMID 41994868,siRNA,TTR,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Analysis of miRNA-like off-target activity in a luciferase reporter assay; paragraph 3,1031,Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.,41994868,PMC13096799,10.1093/nar/gkag345,https://pubmed.ncbi.nlm.nih.gov/41994868/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The greatest impact of SNA modification was observed when included at position g7 in si-50, with a relative off-target IC50 increase of ~260-fold over the parent si-47.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,2,siVIM-270 chemical modification panel from PMID 41467115,siRNA,VIM,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > RNAi and off-target activities of siRNAs with chemical modifications; paragraph 10,1157,An siRMSD parameter of structural distortion induced by chemical modification is predictive of the off-target effect of siRNA.,41467115,PMC12744844,10.1016/j.omtn.2025.102693,https://pubmed.ncbi.nlm.nih.gov/41467115/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The effects on off-target genes were validated by microarray and RT-qPCR analyses.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,3,RGLS4326,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > RGLS4326 inhibits AMPAR ligand binding and function; paragraph 10,1410,The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.,41315228,PMC12663328,10.1038/s41467-025-65799-5,https://pubmed.ncbi.nlm.nih.gov/41315228/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,devoid of off-target AMPAR interaction and CNS toxicity while preserving the potency against the on-target miR-17.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,4,APP-AON/ATXN3-AON/HTT-AON panel from PMID 41066632,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,Results > Hybridization-dependent off-target splicing events do not play a major role after transfection; paragraph 19,1442,Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells.,41066632,PMC12581821,10.1093/hmg/ddaf153,https://pubmed.ncbi.nlm.nih.gov/41066632/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In this study, we used three different splice-switching AONs targeting three different human transcripts to study their transcriptome-wide, hybridization-dependent off-target effects with short read RNAseq.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,5,PNA-braced ASO panel from PMID 38042877,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,Results > Hybridization-dependent mechanism: complementary PNA strand mitigates off-target hybridizations; paragraph 31,1136,Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.,38042877,PMC10693639,10.1038/s41467-023-43714-0,https://pubmed.ncbi.nlm.nih.gov/38042877/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 38042877; pmc_full_text evidence was direct but less than full primary-detail confidence for hybridization/mismatch off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,6,DM1 ASO panel from PMID 37200862,ASO,DMPK,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > RNA-seq reveals activation of the interferon response by all ASOs and additional off-target effects on gene expression by the repeat gapmer; paragraph 3,1481,Block or degrade? Balancing on- and off-target effects of antisense strategies against transcripts with expanded triplet repeats in DM1.,37200862,PMC10185704,10.1016/j.omtn.2023.04.010,https://pubmed.ncbi.nlm.nih.gov/37200862/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"by performing RNA sequencing (RNA-seq) for cells after ASO treatment, we assessed both on- and off-target effects of the ASOs on a transcriptome-wide level.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,7,ALN-HBV/ALN-HBV02 GalNAc-siRNA panel from PMID 35736224,siRNA,HBV,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,RESULTS > Application of ESC+ design to improve the specificity and safety of ALN-HBV; paragraph 46,1411,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization.,35736224,PMC9262600,10.1093/nar/gkac539,https://pubmed.ncbi.nlm.nih.gov/35736224/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We found that the ESC+ version of ALN-HBV, named ALN-HBV02, with a single GNA substitution at position 6 of the guide strand, and without any further changes in sequence or chemistry, minimizes off-target dysregulation without compromising on-target activity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,8,GalNAc-siRNA panel from PMID 29459660,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > siRNA off-targets are enriched for seed complementarity; paragraph 17,2058,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity.,29459660,PMC5818625,10.1038/s41467-018-02989-4,https://pubmed.ncbi.nlm.nih.gov/29459660/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Consistent with these data, global transcriptome profiling by RNAseq shows RISC loading-dependent downregulation of RNAs enriched for a seed match to the antisense but not the sense strand of GalNAc-siRNAs.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,10,GSK2910546A ASO gapmer panel from PMID 26338776,ASO,BACH1,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,RESULTS > Intronic regions are markedly more susceptible to ASO-silencing than exonic sequence; paragraph 24,2813,In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization.,26338776,PMC4605310,10.1093/nar/gkv857,https://pubmed.ncbi.nlm.nih.gov/26338776/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,We demonstrate in vitro mRNA and protein knockdown of off-targets with a wide range of mismatch (MM) and gap patterns.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,12,siRNA candidate from PMID 41020503,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Modified UNAs mitigate off-target activity without reducing on-target activity in cell culture; paragraph 69,2454,Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.,41020503,PMC12477598,10.1093/nar/gkaf937,https://pubmed.ncbi.nlm.nih.gov/41020503/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 41020503; weak/generic or abstract-limited support for seed-mediated off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,13,ASO candidate from PMID 36229039,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > INRI-seq identifies direct PNA off-targets; paragraph 50,2306,INRI-seq enables global cell-free analysis of translation initiation and off-target effects of antisense inhibitors.,36229039,PMC9825163,10.1093/nar/gkac838,https://pubmed.ncbi.nlm.nih.gov/36229039/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 36229039; weak/generic or abstract-limited support for hybridization/mismatch off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,15,siRNA candidate from PMID 29246303,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > Combination of MOE at Positions 9 and 10 with OMe at Position 14 Diminished or Eliminated Off-Target Effects; paragraph 17,4230,Site-Specific Modification Using the 2'-Methoxyethyl Group Improves the Specificity and Activity of siRNAs.,29246303,PMC5675723,10.1016/j.omtn.2017.10.003,https://pubmed.ncbi.nlm.nih.gov/29246303/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"When the MOE on the guide strand was combined with OMe at position 14 on the passenger strand, the off-target silencing was almost completely eliminated (Figure 8B).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,16,siRNA candidate from PMID 41897327,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,sequence-specificity/off-target evidence,sequence-specificity/off-target evidence,B,3. Results > 3.1. Allele-Specific Silencing Reduces TDP-43 Mislocalization in ALS Motor Neurons; paragraph 21,5621,Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits.,41897327,PMC13024069,10.3390/biom16030393,https://pubmed.ncbi.nlm.nih.gov/41897327/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C as borderline: PMID 41897327; curator counted sequence-specificity/off-target evidence for siRNA candidate from PMID 41897327 despite v2 exclusion. Low-confidence override; v2 note was: Reject under v2: passage supports allele-specific on-target silencing of mutant TDP-43 and cellular phenotype rescue, not observed unintended off-target evidence.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,19,siRNA candidate from PMID 40737088,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Introduction; paragraph 5,1497,Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.,40737088,PMC12309379,10.1093/nar/gkaf692,https://pubmed.ncbi.nlm.nih.gov/40737088/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Importantly, differential gene expression (DGE) analysis showed a significant reduction in off-target effects across in vitro and in vivo, leading to an improved therapeutic profile.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,20,siRNA candidate from PMID 41646886,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Discussion; paragraph 27,1154,2'-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs.,41646886,PMC12870468,10.1016/j.omtn.2026.102835,https://pubmed.ncbi.nlm.nih.gov/41646886/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,we conducted strand-specific RNA sequencing (RNA-seq) to quantify off-target effects of siRNAs bearing,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,21,siRNA candidate from PMID 39813044,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,sequence-specificity/off-target evidence,sequence-specificity/off-target evidence,C,Results and Discussion; paragraph 13,12147,Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.,39813044,PMC12522049manuscript-id: NIHMS2116935,10.1021/acschembio.4c00824,https://pubmed.ncbi.nlm.nih.gov/39813044/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Dual luciferase and RT-qPCR assays in HeLa cells showed that, in a model system of unmodified siRNAs, the amide linkage at position 3 (between nucleosides 3 and 4) suppressed cleavage of off-target YY1 and FADD mRNAs similarly to the industry gold standard modification, glycol nucleic acid (GNA).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,22,siRNA candidate from PMID 39231537,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Results and discussion > Genome-wide evaluation of off-target activities; paragraph 77,12077,Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.,39231537,PMC11472056,10.1093/nar/gkae741,https://pubmed.ncbi.nlm.nih.gov/39231537/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,revealed a significant suppression of off-target activity while maintaining on-target RNAi activity.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,23,siRNA candidate from PMID 35921401,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Results and Discussion > Off-Target Effects of siRNAs Modified with 2′-F/Me; Figure 5 caption,1484,"Role of a ""Magic"" Methyl: 2'-Deoxy-2'-α-F-2'-β-C-methyl Pyrimidine Nucleotides Modulate RNA Interference Activity through Synergy with 5'-Phosphate Mimics and Mitigation of Off-Target Effects.",35921401,PMC9389587,10.1021/jacs.2c01679,https://pubmed.ncbi.nlm.nih.gov/35921401/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,placement of the antisense strand at position 7 mitigated seed-based off-target effects in cell-based assays.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,24,siRNA candidate from PMID 35071927,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Introduction; paragraph 4,2255,siRNA Seed Region Is Divided into Two Functionally Different Domains in RNA Interference in Response to 2'-OMe Modifications.,35071927,PMC8771963,10.1021/acsomega.1c06455,https://pubmed.ncbi.nlm.nih.gov/35071927/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,microarray analysis was performed. Unmodified and modified siVIM-270s were transfected into HeLa cells,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,25,siRNA candidate from PMID 35205363,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,1. Introduction; paragraph 4,2308,The siRNA Off-Target Effect Is Determined by Base-Pairing Stabilities of Two Different Regions with Opposite Effects.,35205363,PMC8872465,10.3390/genes13020319,https://pubmed.ncbi.nlm.nih.gov/35205363/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 35205363; weak/generic or abstract-limited support for seed-mediated off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,26,ASO candidate from PMID 34388351,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,C,Introduction; paragraph 4,2113,Transcriptome-Wide Off-Target Effects of Steric-Blocking Oligonucleotides.,34388351,PMC8713556,10.1089/nat.2020.0921,https://pubmed.ncbi.nlm.nih.gov/34388351/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In this study, we used RNA-seq to evaluate the off-target differential splicing events of 81 SBOs and differential expression events of 46 SBOs.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,27,siRNA candidate from PMID 29450406,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Results and Discussion; paragraph 20,2117,Chemical Modification of the siRNA Seed Region Suppresses Off-Target Effects by Steric Hindrance to Base-Pairing with Targets.,29450406,PMC5808362,10.1021/acsomega.7b00291,https://pubmed.ncbi.nlm.nih.gov/29450406/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Microarray analysis was performed to examine the genome-wide off-target effects of siRNAs modified with DNA, PS, 2′-OMe, and LNA (Figure 2b).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,28,siRNA candidate from PMID 21687525,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,Abstract; paragraph 1,2246,In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts.,21687525,PMC3109444,10.4161/adna.1.1.12204,https://pubmed.ncbi.nlm.nih.gov/21687525/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, the level of off-target gene regulation in both the tumor and the liver correlated with the increase in efficacy in target knockdown, unless the seed region of the siRNA was modified.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,33,ADO2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Discussion; paragraph 15,3759,Development and evaluation of siRNA-mediated gene silencing strategies for ADO2 therapy utilizing iPSCs model and DMPC-SPIONs delivery system.,39934917,PMC11816505,10.1186/s13287-025-04151-6,https://pubmed.ncbi.nlm.nih.gov/39934917/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C as borderline: PMID 39934917; curator counted seed-mediated off-target effect for ADO2 despite v2 exclusion. Low-confidence override; v2 note was: Observed result is allele/on-target mutant CLCN7 silencing specificity, while off-target text is background/design discussion; no measured unintended off-target effect.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,36,CCND1; Drisapersen; Mipomersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,Discussion; paragraph 62,2210,"Single Stranded Fully Modified-Phosphorothioate Oligonucleotides can Induce Structured Nuclear Inclusions, Alter Nuclear Protein Localization and Disturb the Transcriptome In Vitro.",35464859,PMC9019733,10.3389/fgene.2022.791416,https://pubmed.ncbi.nlm.nih.gov/35464859/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Here, we report chemistry-specific effects of oligonucleotides composed of modified or unmodified bases, with phosphorothioate linkages, on subnuclear organelles and show altered distribution of nuclear proteins, the appearance of highly stable and strikingly structured nuclear inclusions, and disturbed RNA processing in primary human fibroblasts and other cultured cells.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,40,SPC2996; PC3; CaCo2,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,A,RESULTS AND DISCUSSION > Gene silencing by gymnotic delivery is a general phenomenon; paragraph 15,2845,"Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents.",19854938,PMC2800216,10.1093/nar/gkp841,https://pubmed.ncbi.nlm.nih.gov/19854938/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 19854938; pmc_full_text evidence was direct but less than full primary-detail confidence for off-target evidence.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,42,TNRC6; GW182; AGO2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,PubMed abstract,1011,Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates.,40134378,,10.1089/nat.2024.0090,https://pubmed.ncbi.nlm.nih.gov/40134378/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"We demonstrate that knocking down AGO2, but not AGO1 or AGO4, is protective against GalNAc-siRNA-driven off-target activity and hepatotoxicity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,44,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,PubMed abstract,2193,Alteration of target cleavage patterns and off-target reduction of antisense oligonucleotides incorporating 2-N-carbamoyl- or (2-pyridyl)guanine.,37310350,,10.1039/d3ob00574g,https://pubmed.ncbi.nlm.nih.gov/37310350/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"We conducted ultraviolet (UV) melting experiments, RNase H cleavage assays, in vitro knockdown assays, and off-target transcriptome analyses using DNA microarrays.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,47,unspecified antisense oligonucleotide,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,PubMed abstract,2216,Using RNA-seq to Assess Off-Target Effects of Antisense Oligonucleotides in Human Cell Lines.,33314011,,10.1007/s40291-020-00504-4,https://pubmed.ncbi.nlm.nih.gov/33314011/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,METHODS: We extend recent studies by investigating the off-target profile of two 17-mer antisense oligonucleotides in two distinct human cell lines by a whole-transcriptome study using RNA sequencing.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,49,siF12; siF12-A; siF12-AC9,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,PubMed abstract,12115,"Use of ""C9/11 Mismatch"" Control siRNA Reveals Sequence-Related Off-Target Effect on Coagulation of an siRNA Targeting Mouse Coagulation Factor XII.",31063435,,10.1089/nat.2018.0767,https://pubmed.ncbi.nlm.nih.gov/31063435/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,As this change in coagulation was unrelated to FXII we conclude that it was off-target.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,50,Malat1-targeting,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,PubMed abstract,12059,Role of Computationally Evaluated Target Specificity in the Hepatotoxicity of Gapmer Antisense Oligonucleotides.,30095329,,10.1089/nat.2018.0724,https://pubmed.ncbi.nlm.nih.gov/30095329/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Transcriptome analysis indicated that nontoxic gapmers do not cleave off-target RNAs, although they have many target-like RNA sequences.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,51,ARL4C; ARL4C-targeting; CP8,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,PubMed abstract,1037,Development of ARL4C antisense oligonucleotide with reduced off-target effects and enhanced efficacy as an anti-cancer drug.,41792408,,10.1007/s11626-026-01154-2,https://pubmed.ncbi.nlm.nih.gov/41792408/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"ASO-2025-A/L downregulated 317 genes, which were confirmed by RNA-sequence analysis, the majority was involved in cell adhesion pathways downstream of ARL4C signaling, and only two genes corresponded to off-target genes.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,56,PDIA3; oblimersen,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,PubMed abstract,2270,Off-target effects related to the phosphorothioate modification of nucleic acids.,20544786,,10.1002/cmdc.201000156,https://pubmed.ncbi.nlm.nih.gov/20544786/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Regardless of their target, phosphorothioate-modified antisense and siRNA compounds, but not oligonucleotides with a phosphodiester backbone, resulted in a similar impact on the proteome.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,59,"ASO 6 (recovered B2 from PMID:40672232, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,RESULTS > RNP delivery reduces transcriptome-wide off-target editing; paragraph 22,1824,Targeted RNA editing by direct delivery of an adenosine deaminase-antisense oligo conjugate.,40672232,PMC12265680,10.1101/2025.07.11.664364,https://pubmed.ncbi.nlm.nih.gov/40672232/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Further, we demonstrate that a covalent adenosine deaminase-ASO “RNP” conjugate formed in the test tube and delivered by lipofection achieves targeted and efficient RNA editing with dramatically lower transcriptome-wide off-target editing as compared to ectopically expressed RNA editing enzymes.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,60,siRNA-based,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Minimal off-target activity of GalNAc-siCIDEB; paragraph 8,9324,Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models.,40503175,PMC12156227,10.1016/j.omtn.2025.102567,https://pubmed.ncbi.nlm.nih.gov/40503175/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To evaluate the off-target effects of GalNAc-siCIDEB, we first conducted whole-transcriptome RNA sequencing (RNA-seq) analysis in primary rat hepatocytes.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,62,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,RESULTS > Impact of GNA isonucleotides on GalNAc-siRNA in vitro activity; paragraph 49,2309,Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs.,34648028,PMC8565336,10.1093/nar/gkab916,https://pubmed.ncbi.nlm.nih.gov/34648028/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted B->C: PMID 34648028; weak/generic or abstract-limited support for seed-mediated off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,63,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Transcriptome-wide analyses of mi/siRNAs targeting E6/E7; paragraph 17,12558,AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.,33664996,PMC7900643,10.1016/j.omtn.2021.01.018,https://pubmed.ncbi.nlm.nih.gov/33664996/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Accept C as borderline: PMID 33664996; curator counted seed-mediated off-target effect for siRNAs despite v2 exclusion. Low-confidence override; v2 note was: The paper intentionally designs siRNAs to exploit tumor-suppressive miRNA-like seed activity and reports anticancer efficacy; this is not observed unintended off-target?,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,64,unspecified siRNA (PMID:31375812),siRNA,,,,,,,,,,,,unspecified,unspecified,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Di-siRNA modulates HTT expression with minimal off-target events; paragraph 33,4213,A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.,31375812,PMC6879195manuscript-id: NIHMS1533065,10.1038/s41587-019-0205-0,https://pubmed.ncbi.nlm.nih.gov/31375812/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To determine if HTT silencing or Di-siRNA treatment had any major effect on the transcriptome, we performed genome-wide RNA sequencing (RNA-seq), comparing Di-siRNAHTT-treated to naïve NHP brains. We analyzed three cortical replicates from each of 8 animals (4 naïve, 4 treated). We chose to analyze the cortex, because we observed the highest accumulation of Di-siRNA in this region. Therefore, the chances of seeing off-target effects would be maximized.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,65,unspecified ASO (PMID:29390093),ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,RESULTS > Hybridization-dependent toxicity is not likely to account for the 2′ F PS-ASO-induced hepatotoxicity; Figure 5. caption,2060,Acute hepatotoxicity of 2' fluoro-modified 5-10-5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins.,29390093,PMC5861398,10.1093/nar/gky060,https://pubmed.ncbi.nlm.nih.gov/29390093/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 29390093; pmc_full_text evidence was direct but less than full primary-detail confidence for transcriptome-level off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,66,"Sequence 1 (recovered B2 from PMID:28918038, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > High Confirmation Rate of In Silico Predicted OTEs in Mouse Liver; paragraph 14,2064,Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs.,28918038,PMC5537172,10.1016/j.omtn.2017.07.003,https://pubmed.ncbi.nlm.nih.gov/28918038/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Furthermore, to study the underlying mechanisms of liver toxicity, we applied transcriptome profiling and pathway analyses and show that adverse in vivo liver phenotypes correlate with the number of potent, hybridization-mediated off-target effects (OTEs).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,67,LNA ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,RESULTS > Hepatotoxicity of LNA ASOs is RNase H1 dependent; paragraph 35,2062,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.,26553810,PMC4797265,10.1093/nar/gkv1210,https://pubmed.ncbi.nlm.nih.gov/26553810/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,73,designated ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,PubMed abstract,1453,Preclinical toxicological assessment of amido-bridged nucleic acid-modified antisense oligonucleotides targeting synaptotagmin XIII for intra-abdominal treatment of peritoneal metastasis of gastric cancer.,39192097,,10.1007/s10120-024-01548-9,https://pubmed.ncbi.nlm.nih.gov/39192097/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"In rats, off-target toxicity (not attributable to hybridization) was observed after weekly intra-abdominal administration of ASO-4733.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,78,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > ASO off-target RNA reduction correlates well with off-target protein reduction in HepG2 cells; paragraph 48,1035,Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach.,41918821,PMC13034028,10.1093/narmme/ugag016,https://pubmed.ncbi.nlm.nih.gov/41918821/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Furthermore, many OffT effects observed at the RNA level do not directly translate to corresponding protein level changes.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,82,"siRNA-IGF2BP2 (recovered B2 from PMID:41859644, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > IGF2BP2 Knockdown promotes ferroptosis in HNSCC via reduced NRF2 mRNA stability; paragraph 10,1732,An exosome-biomimetic photothermal nanocarrier for IGF2BP2 siRNA delivery and enhanced ferroptosis in head and neck squamous cell carcinoma.,41859644,PMC12996677,10.1016/j.mtbio.2026.102999,https://pubmed.ncbi.nlm.nih.gov/41859644/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To assess siRNA specificity, we performed seed-based 3′UTR off-target prediction and integrated it with the RNA-seq dataset; no enrichment of predicted off-target transcripts among genes with significantly downregulated expressions was observed.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,91,"S9 (recovered B2 from PMID:41552385, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,Results > Screening of SNA-modified siRNAs targeting CAG repeats; paragraph 8,3301,An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.,41552385,PMC12804371,10.1016/j.omtn.2025.102802,https://pubmed.ncbi.nlm.nih.gov/41552385/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C as borderline: PMID 41552385; curator counted hybridization/mismatch off-target effect for siRNA despite v2 exclusion. Low-confidence override; v2 note was: reject: central mismatch/SNA assays measure allele-selective knockdown of expanded versus normal CAG targets, not unintended off-target hybridization effects",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,113,unspecified siRNA (PMID:40385635),siRNA,,,,,,,,,,,,unspecified,unspecified,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > In silico off-target analysis and qPCR validation; paragraph 10,1477,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen.",40385635,PMC12083919,10.1016/j.omtn.2025.102542,https://pubmed.ncbi.nlm.nih.gov/40385635/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Subsequently, the knockdown efficiency of candidate siRNAs on these potential off-target genes was individually verified through in-vitro qPCR. Most candidate siRNAs exhibited little potential off-target effects on those genes (Figures S10 and S11). However, two siRNAs, si098-DV29P and si086-DV26P, exerted relatively strong inhibition on their potential off-target genes (Figures S10B and S10E), suggesting that measures should be taken to prevent and control the off-target risk.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,115,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,A,2. Results > 2.4. Gene Silencing Effect of Chemically Modified siRNAs; paragraph 14,1788,Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.,41373822,PMC12692593,10.3390/ijms262311675,https://pubmed.ncbi.nlm.nih.gov/41373822/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, siRNA 27 treatment led to increased expression of IFIT1 (Figure 7A) and OAS1 (Figure 7B), and siRNA 30 induced elevated expression of IFIT1 (Figure 7A), OAS1 (Figure 7B), and ISG20 (Figure 7D).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,116,unspecified siRNA (PMID:41341748),siRNA,,,,,,,,,,,,unspecified,unspecified,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Characterization of off-target activities of bsYW-61; paragraph 14,1789,A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand.,41341748,PMC12670904,10.1016/j.omtn.2025.102768,https://pubmed.ncbi.nlm.nih.gov/41341748/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"bsYW-61 reduced luciferase activity in the guide strand seed reporter, confirming seed-mediated off-target effects (Figure 6I). In contrast, modified bsYW-61m1 showed no such activity, suggesting that the chemical modification effectively abolished these interactions.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,135,siNTC,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > Transcriptomic analyses of BHF7-transfected vSMCs demonstrates expected changes to known SMILR regulated genes without apparent toxic effect; paragraph 43,8415,Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure.,40928446,PMC12790151,10.1016/j.jacbts.2025.101364,https://pubmed.ncbi.nlm.nih.gov/40928446/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40928446; pmc_full_text evidence was direct but less than full primary-detail confidence for transcriptome-level off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,144,unspecified siRNA (PMID:40142497),miRNA agomir,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,B,Abstract; paragraph 1,9881,In Vitro Transcribed Artificial Primary MicroRNA for the Inhibition of Hepatitis B Virus Gene Expression in Cultured Cells.,40142497,PMC11946339,10.3390/microorganisms13030604,https://pubmed.ncbi.nlm.nih.gov/40142497/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Activation of the interferon response may cause non-specific inhibition of gene expression and could explain the observed non-specific effects of in vitro transcribed pri-miR-31 sequences.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,157,"Anti-N1 (recovered B2 from PMID:38379891, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results; paragraph 9,1592,Synergistic Effect of an Antisense Oligonucleotide and Small Molecule on Splicing Correction of the Spinal Muscular Atrophy Gene.,38379891,PMC10878212,10.1177/26331055241233596,https://pubmed.ncbi.nlm.nih.gov/38379891/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"To determine whether combination treatment exacerbates the off-target effects of the individual compounds, we performed RNA-Seq on transcripts isolated from cells treated with LoA + R and LoA + B (Figure 2A and B).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,164,"PH-762 (recovered B2 from PMID:39697325, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > PH-762 is a stabilized self-delivering siRNA compound designed to potently silence PDCD1 mRNA with high specificity; paragraph 10,10539,Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy.,39697325,PMC11652358,10.3389/fimmu.2024.1501679,https://pubmed.ncbi.nlm.nih.gov/39697325/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The in silico predictions were confirmed experimentally in CD3/CD28 bead-activated human pan T cells, where no off-target silencing GRAMD4 mRNA was observed, such that an IC50 for PH-762 toward GRAMD4 mRNA could not be determined",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,188,"Glu-CT102MOE5 (recovered B2 from PMID:37251692, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,A,Results > Transcriptomics and proteomics analysis of modified CT102s; paragraph 23,14112,Modified ASO conjugates encapsulated with cytidinyl/cationic lipids exhibit more potent and longer-lasting anti-HCC effects.,37251692,PMC10220282,10.1016/j.omtn.2023.04.028,https://pubmed.ncbi.nlm.nih.gov/37251692/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Also, they could interact with other mRNAs via imperfect matches (such as GAS2, POLA2, and LGALS2), thereby downregulating the expression of the related proteins and jointly inducing the apoptotic process of tumor cells (Table S4).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,190,"si-S1A3-Chol (recovered B2 from PMID:36618268, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,seed-mediated off-target effect,seed-mediated off-target effect,A,Results > Off-target effect analysis; paragraph 18,14301,Chemically modified small interfering RNA targeting Hedgehog signaling pathway for rheumatoid arthritis therapy.,36618268,PMC9813581,10.1016/j.omtn.2022.12.008,https://pubmed.ncbi.nlm.nih.gov/36618268/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"As the RNA-seq results demonstrated, the off-target rate of si-S1A3-Chol was less than that of naked siRNA, which usually ranges from 5% to 80%.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,193,unspecified ASO (PMID:36511872),ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,RESULTS > Indirect FXN activation is unlikely to be mediated by a mutual hybridization-dependent off-target transcript; paragraph 49,2253,G-rich motifs within phosphorothioate-based antisense oligonucleotides (ASOs) drive activation of FXN expression through indirect effects.,36511872,PMC9825156,10.1093/nar/gkac1108,https://pubmed.ncbi.nlm.nih.gov/36511872/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->C: PMID 36511872; weak/generic or abstract-limited support for transcriptome-level off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,201,siRNAs,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,RESULTS AND DISCUSSION > On-target and off-target activities of siRNAs modified with 2′-F-NMC; paragraph 42,4163,siRNAs containing 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2'-F-NMC NTPs.,33577685,PMC7969009,10.1093/nar/gkab050,https://pubmed.ncbi.nlm.nih.gov/33577685/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The off-target activities of the parent duplex and the modified duplexes were similar (Figure 5B).,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,207,"T39 ASO (recovered B2 from PMID:32180554, curator:CM)",ASO,,,,,,,,,,,,unspecified,unspecified,off-target evidence,off-target evidence,A,Results > ASOs targeting human mRNAs can also induce a type I IFN response in cultured THP1 cells; paragraph 31,2770,Antisense oligonucleotide treatment produces a type I interferon response that protects against diet-induced obesity.,32180554,PMC7036698,10.1016/j.molmet.2020.01.010,https://pubmed.ncbi.nlm.nih.gov/32180554/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"RNA-seq analysis of gWAT showed a widespread increase in type I interferon (IFN)-responsive genes, and knockout of the IFN receptor abolished the weight loss phenotype induced by the T39 ASO.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,217,"unspecified ASO (v1 extraction artefact, pending source re-verification)",ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,"Results > QR-110 Treatment Reduces Aberrant Splicing, Increases Wild-Type CEP290 in Homozygous Retinal Organoids, and Shows No Off-Target Pharmacology; paragraph 15",12621,Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.,30114557,PMC6092551,10.1016/j.omtn.2018.07.010,https://pubmed.ncbi.nlm.nih.gov/30114557/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We also performed RNA-sequencing (RNA-seq) to complement this sequence homology-based study with an unbiased approach and identify other potential hybridization-dependent off-targets. Transcriptome analysis was performed to assess the hybridization-dependent off-target effects using two untreated and two 1 μM QR-110-treated LCA10 retinal organoids. This dose was selected because it was effective at suppressing exon X (Figure 3), suggesting effective hybridization and blocking activity, but it did not significantly increase CEP290 26-27 mRNA (Figure 3F). Therefore, increased levels of CEP290 mRNA, such as those observed at higher concentrations of QR-110, which could have wider, downstream “on-target” effects, would not confound the identification of genuine “off-target” effects. Using a 2-fold change as a cutoff, 44 differentially expressed genes were identified, but none has complementarity to QR-110 (Table S8). This number of differential genes in QR-110-treated organoids is similar to transcriptome changes observed for other antisense oligonucleotides and small-molecule drugs.27 Importantly, none of the seven downregulated genes have been associated with retinal dysfunction. In combination with the selected gene analyses, these data suggest QR-110 does not have any major off-target activity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,220,unspecified siRNA (PMID:27461380),ASO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results > Off-target knockdown by the Acsl1 gapmer; paragraph 15,2061,Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides.,27461380,PMC4961955,10.1038/srep30377,https://pubmed.ncbi.nlm.nih.gov/27461380/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Microarray analysis revealed that several pre-mRNAs containing a sequence similar to the gapmer target were also knocked down. These results suggest that hepatotoxicity of LNA gapmer is caused by RNAseH1 activity, presumably because of off-target cleavage of RNAs inside nuclei.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,222,"FM10 (recovered B2 from PMID:27378237, curator:CM)",PMO,,,,,,,,,,,,unspecified,unspecified,transcriptome-level off-target effect,transcriptome-level off-target effect,A,Results; paragraph 9,15206,Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics.,27378237,PMC5023379,10.1038/mt.2016.111,https://pubmed.ncbi.nlm.nih.gov/27378237/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"RNA-seq analysis of FM10 myotube cultures from the two unaffected first-degree relatives provides another view of off-target effects, unclouded by DUX4 target genes, as unaffected cells express little if any DUX4-fl. For these cells, only three genes differed significantly between FM10 and the control PMO (P-value < 10–4), and this is roughly what one expects by chance when testing ~37,000 genes for differential expression, even if the null hypotheses of equal expression are all true (Figure 2c). No genes had P-value < 10−5 or false discovery rate < 0.72. Thus we observed no clear off-target effects of FM10 based on these samples.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,229,"MC3 LNP-siRNA (recovered B2 from PMID:41708903, curator:CM)",siRNA,,,,,,,,,,,,unspecified,unspecified,off-target evidence,off-target evidence,B,PubMed abstract,1209,Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.,41708903,,10.1007/s13346-026-02076-y,https://pubmed.ncbi.nlm.nih.gov/41708903/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, the MC3-based LNP-siRNA (MC3 LNP-siRNA) treatment elicited the least off-target immune activation, with no induction of interferon stimulated genes. Additionally, the MC3 LNP-siRNA remained effective when administered 24 h post-infection, significantly reducing viral RNA levels in vitro. Chemical modification of siRNA with 2'‑O‑methyl incorporation further attenuated immune activation, without compromising efficacy.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,275,nusinersen,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,PubMed abstract,28702,High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.,34445083,PMC8395096,10.3390/ijms22168378,https://pubmed.ncbi.nlm.nih.gov/34445083/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for transcriptome-level off-target effect in nusinersen; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,281,bulge-siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,C,PubMed abstract,15373,Modified siRNA structure with a single nucleotide bulge overcomes conventional siRNA-mediated off-target silencing.,21673662,PMC3182346,10.1038/mt.2011.109,https://pubmed.ncbi.nlm.nih.gov/21673662/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for seed-mediated off-target effect in bulge-siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,331,F7-1 siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Enrichment analysis of seed region matches in F7-1 off-target genes; paragraph 13,15845,Single base mismatches in the mRNA target site allow specific seed region-mediated off-target binding of siRNA targeting human coagulation factor 7.,22258146,PMC3342946,10.4161/rna.9.1.18121,https://pubmed.ncbi.nlm.nih.gov/22258146/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for seed-mediated off-target effect in F7-1 siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,333,ATXN3-AON,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Hybridization-dependent off-target splicing events do not play a major role after transfection; paragraph 19,1442,Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells.,41066632,PMC12581821,10.1093/hmg/ddaf153,https://pubmed.ncbi.nlm.nih.gov/41066632/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In this study, we used three different splice-switching AONs targeting three different human transcripts to study their transcriptome-wide, hybridization-dependent off-target effects with short read RNAseq.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,334,modified duplex,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > In vitro gene silencing of modified siRNA containing SNA modifications; paragraph 28,1031,Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.,41994868,PMC13096799,10.1093/nar/gkag345,https://pubmed.ncbi.nlm.nih.gov/41994868/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The greatest impact of SNA modification was observed when included at position g7 in si-50, with a relative off-target IC50 increase of ~260-fold over the parent si-47.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,337,UNA-T siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > Global off-target analysis; paragraph 23,15362,Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs.,21047800,PMC3061082,10.1093/nar/gkq961,https://pubmed.ncbi.nlm.nih.gov/21047800/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for seed-mediated off-target effect in UNA-T siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,338,siCD46 siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Comparison of site-specific alterations in siRNA or target sequence; paragraph 15,15336,Analysis of siRNA specificity on targets with double-nucleotide mismatches.,18420656,PMC2396434,10.1093/nar/gkn190,https://pubmed.ncbi.nlm.nih.gov/18420656/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hybridization/mismatch off-target effect in siCD46 siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,339,BTK siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > A 7 nt complementation between the original GRK4(O)/BTK(O) siRNAs and the hif-1α mRNA triggers the degradation of hif-1α mRNA; paragraph 15,20894,siRNA-mediated off-target gene silencing triggered by a 7 nt complementation.,16091630,PMC1184219,10.1093/nar/gki762,https://pubmed.ncbi.nlm.nih.gov/16091630/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for seed-mediated off-target effect in BTK siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,340,GR18-3 ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Comparative Analysis of Off-Target Effects; paragraph 23,28684,Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension.,34994962,PMC8766371,10.1007/s40291-021-00573-z,https://pubmed.ncbi.nlm.nih.gov/34994962/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for hybridization/mismatch off-target effect in GR18-3 ASO; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,343,SOD-1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Higher order structure of the SOD-1 minigene mRNA significantly influences ASO binding; paragraph 27,31422,Defining the factors that contribute to on-target specificity of antisense oligonucleotides.,25072142,PMC4114480,10.1371/journal.pone.0101752,https://pubmed.ncbi.nlm.nih.gov/25072142/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hybridization/mismatch off-target effect in SOD-1; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,344,VIR-2218,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > Application of ESC+ design to improve the specificity and safety of ALN-HBV; paragraph 46,1411,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization.,35736224,PMC9262600,10.1093/nar/gkac539,https://pubmed.ncbi.nlm.nih.gov/35736224/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We found that the ESC+ version of ALN-HBV, named ALN-HBV02, with a single GNA substitution at position 6 of the guide strand, and without any further changes in sequence or chemistry, minimizes off-target dysregulation without compromising on-target activity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,345,siRNA-5,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > siRNA off-targets are enriched for seed complementarity; paragraph 17,2058,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity.,29459660,PMC5818625,10.1038/s41467-018-02989-4,https://pubmed.ncbi.nlm.nih.gov/29459660/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Consistent with these data, global transcriptome profiling by RNAseq shows RISC loading-dependent downregulation of RNAs enriched for a seed match to the antisense but not the sense strand of GalNAc-siRNAs.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,346,LNA-PS ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Intronic regions are markedly more susceptible to ASO-silencing than exonic sequence; paragraph 24,2813,In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization.,26338776,PMC4605310,10.1093/nar/gkv857,https://pubmed.ncbi.nlm.nih.gov/26338776/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,We demonstrate in vitro mRNA and protein knockdown of off-targets with a wide range of mismatch (MM) and gap patterns.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,348,siRNA-604,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Rational design of allele-specific siRNA using the mismatch discrimination model as a guide; paragraph 20,15837,Profiling of mismatch discrimination in RNAi enabled rational design of allele-specific siRNAs.,19815667,PMC2794185,10.1093/nar/gkp835,https://pubmed.ncbi.nlm.nih.gov/19815667/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for hybridization/mismatch off-target effect in siRNA-604; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,351,siVIM-270,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > RNAi and off-target activities of siRNAs with chemical modifications; paragraph 10,1157,An siRMSD parameter of structural distortion induced by chemical modification is predictive of the off-target effect of siRNA.,41467115,PMC12744844,10.1016/j.omtn.2025.102693,https://pubmed.ncbi.nlm.nih.gov/41467115/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,The effects on off-target genes were validated by microarray and RT-qPCR analyses.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,355,DM1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,Results > The repeat-blocking ASO and both gapmers lead to downregulation of DMPK RNA; paragraph 8,1481,Block or degrade? Balancing on- and off-target effects of antisense strategies against transcripts with expanded triplet repeats in DM1.,37200862,PMC10185704,10.1016/j.omtn.2023.04.010,https://pubmed.ncbi.nlm.nih.gov/37200862/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"by performing RNA sequencing (RNA-seq) for cells after ASO treatment, we assessed both on- and off-target effects of the ASOs on a transcriptome-wide level.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,364,siCdc2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > Combination of MOE at Positions 9 and 10 with OMe at Position 14 Diminished or Eliminated Off-Target Effects; paragraph 17,4230,Site-Specific Modification Using the 2'-Methoxyethyl Group Improves the Specificity and Activity of siRNAs.,29246303,PMC5675723,10.1016/j.omtn.2017.10.003,https://pubmed.ncbi.nlm.nih.gov/29246303/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"When the MOE on the guide strand was combined with OMe at position 14 on the passenger strand, the off-target silencing was almost completely eliminated (Figure 8B).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,370,60 siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > siPools affect global transcript levels less than single siRNAs; Figure 4. caption,16582,siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.,24875475,PMC4081087,10.1093/nar/gku480,https://pubmed.ncbi.nlm.nih.gov/24875475/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for seed-mediated off-target effect in 60 siRNA; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,383,siEGFP1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > siRNA titrations reveal reduced off-targeting by siRNA UNA modification; paragraph 13,15558,A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects.,20453030,PMC2943616,10.1093/nar/gkq341,https://pubmed.ncbi.nlm.nih.gov/20453030/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept B: PubMed abstract gives a direct abstract-level signal for seed-mediated off-target effect in siEGFP1; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,384,Ago2; Ago1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > Ago2 is not required for PIK3CB off-target and some on-target siRNA activity; paragraph 15,15470,Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 'Slicer' independent and can be mediated by Ago1.,19767612,PMC2777430,10.1093/nar/gkp735,https://pubmed.ncbi.nlm.nih.gov/19767612/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for seed-mediated off-target effect in Ago2; Ago1; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,386,TNFR1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > 736 SENSE STRAND ACTIVITY IS INHIBITED BY CHEMICAL AND SEQUENCE MODIFICATION; paragraph 30,21536,Knockdown of TNFR1 by the sense strand of an ICAM-1 siRNA: dissection of an off-target effect.,18096615,PMC2275081,10.1093/nar/gkm630,https://pubmed.ncbi.nlm.nih.gov/18096615/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Accept C: PubMed abstract gives a weak abstract-level signal for seed-mediated off-target effect in TNFR1; no full passage, so curator kept confidence limited.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,390,TS1-ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Identification of potential nucleobase modifications that reduce LNA gapmer hepatotoxicity; Figure 2. caption,1409,Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.,35801870,PMC9303313,10.1093/nar/gkac562,https://pubmed.ncbi.nlm.nih.gov/35801870/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,This means that there is no clear correlation between the changes in the off-target effects and the hepatotoxicity observed with the introduction of nucleobase modification.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,391,S10-1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Indirect FXN activation is unlikely to be mediated by a mutual hybridization-dependent off-target transcript; paragraph 49,2253,G-rich motifs within phosphorothioate-based antisense oligonucleotides (ASOs) drive activation of FXN expression through indirect effects.,36511872,PMC9825156,10.1093/nar/gkac1108,https://pubmed.ncbi.nlm.nih.gov/36511872/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->C: PMID 36511872; weak/generic or abstract-limited support for hybridization/mismatch off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,392,LNA ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Hepatotoxicity of LNA ASOs is RNase H1 dependent; paragraph 35,2062,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.,26553810,PMC4797265,10.1093/nar/gkv1210,https://pubmed.ncbi.nlm.nih.gov/26553810/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,394,TMEM16a,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > TMEM16a ASO is specific and not toxic; paragraph 12,1233,Restoring chloride efflux in cystic fibrosis with TMEM16a antisense oligonucleotides.,40926414,PMC12703169,10.1016/j.ymthe.2025.08.045,https://pubmed.ncbi.nlm.nih.gov/40926414/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,No notable adverse drug binding of TMEM16a ASO was observed,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,411,PS-ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,RESULTS > Hybridization-dependent toxicity is not likely to account for the 2′ F PS-ASO-induced hepatotoxicity; Figure 5. caption,2060,Acute hepatotoxicity of 2' fluoro-modified 5-10-5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins.,29390093,PMC5861398,10.1093/nar/gky060,https://pubmed.ncbi.nlm.nih.gov/29390093/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"based on analysis of the microarray data, none of the potential off-target transcripts were reduced by >50%",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,414,CD-1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,RESULTS > Evaluation of hepatotoxicity in mice; paragraph 14,2063,Sequence motifs associated with hepatotoxicity of locked nucleic acid--modified antisense oligonucleotides.,24550163,PMC4005641,10.1093/nar/gku142,https://pubmed.ncbi.nlm.nih.gov/24550163/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The P53 and Nrf2/ARE reporters were substantially induced by compound 3 but not by 1a or 1b, suggesting these pathways may be associated with motif-related hepatotoxicity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,415,WRN-108,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Translational activity in non-human primates; paragraph 29,1055,Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.,42095135,PMC13140060,10.1016/j.omtn.2026.102930,https://pubmed.ncbi.nlm.nih.gov/42095135/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"expression levels of HHLA2, GRHL2, and DPP10 were unchanged compared with vehicle-treated controls",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,416,KCNT1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,Results > KCNT1-knockdown-ASO screening in cell lines and patient iPSC-derived neurons; paragraph 8,1058,Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.,41981306,PMC13099374,10.1038/s41591-026-04314-9,https://pubmed.ncbi.nlm.nih.gov/41981306/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,We used RNA sequencing (RNA-seq) to perform transcriptome-wide analysis of gene expression patterns in human iPSC-derived neurons before and after gymnotic treatment and found none of these potential targets to be significantly perturbed by KT777,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,417,HIV-1,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Study of antiretroviral activity; paragraph 38,1210,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1.,41704705,PMC12907196,10.3389/fmed.2026.1719202,https://pubmed.ncbi.nlm.nih.gov/41704705/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,oligonucleotide with a mismatched sequence,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,436,ASO-001933,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Initial tiling screen identified a parental ASO targeting the 3′ UTR of MAPT with high cross-species reactivity; paragraph 6,1615,Identification and characterization of a MAPT-targeting locked nucleic acid antisense oligonucleotide therapeutic for tauopathies.,36090761,PMC9424863,10.1016/j.omtn.2022.07.027,https://pubmed.ncbi.nlm.nih.gov/36090761/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Our RNA-seq data revealed that MAPT is the only differentially regulated gene,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,441,T39 ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > ASOs targeting human mRNAs can also induce a type I IFN response in cultured THP1 cells; paragraph 31,2770,Antisense oligonucleotide treatment produces a type I interferon response that protects against diet-induced obesity.,32180554,PMC7036698,10.1016/j.molmet.2020.01.010,https://pubmed.ncbi.nlm.nih.gov/32180554/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,strongly suggesting an off-target effect of the T39 ASO,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,451,IGF2BP2,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > IGF2BP2 Knockdown promotes ferroptosis in HNSCC via reduced NRF2 mRNA stability; paragraph 10,1732,An exosome-biomimetic photothermal nanocarrier for IGF2BP2 siRNA delivery and enhanced ferroptosis in head and neck squamous cell carcinoma.,41859644,PMC12996677,10.1016/j.mtbio.2026.102999,https://pubmed.ncbi.nlm.nih.gov/41859644/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,no enrichment of predicted off-target transcripts among genes with significantly downregulated expressions was observed,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,456,modified siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Screening of SNA-modified siRNAs targeting CAG repeats; paragraph 8,3301,An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.,41552385,PMC12804371,10.1016/j.omtn.2025.102802,https://pubmed.ncbi.nlm.nih.gov/41552385/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"In the first reporter assay using the AR28Q or AR54Q vectors, REP suppressed both the AR28Q and AR54Q proteins, whereas P9, S9, P9S9, P9S10, and P9S910 selectivity suppressed the AR54Q protein (Figure S1C).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,462,si098-DV29P,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > In vivo silencing of AGT by GalNAc-siRNAs; paragraph 13,1477,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen.",40385635,PMC12083919,10.1016/j.omtn.2025.102542,https://pubmed.ncbi.nlm.nih.gov/40385635/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"However, two siRNAs, si098-DV29P and si086-DV26P, exerted relatively strong inhibition on their potential off-target genes (Figures S10B and S10E), suggesting that measures should be taken to prevent and control the off-target risk.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,463,YAP1; WWTR1,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Characterization of off-target activities of bsYW-61; paragraph 14,1789,A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand.,41341748,PMC12670904,10.1016/j.omtn.2025.102768,https://pubmed.ncbi.nlm.nih.gov/41341748/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"bsYW-61 reduced luciferase activity in the guide strand seed reporter, confirming seed-mediated off-target effects (Figure 6I).",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,464,ACTB ASO,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,RESULTS > RNP delivery reduces transcriptome-wide off-target editing; paragraph 22,1824,Targeted RNA editing by direct delivery of an adenosine deaminase-antisense oligo conjugate.,40672232,PMC12265680,10.1101/2025.07.11.664364,https://pubmed.ncbi.nlm.nih.gov/40672232/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,transcriptome-wide off-target editing events as compared to plasmid-based expression of TadA8.20-HaloTag.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,473,UU-3,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,off-target evidence,off-target evidence,B,Results > Synthesis of a Cond-siRNA construct based on RNA sensor Nppa and target gene calcineurin; paragraph 11,3544,Development of conditional-siRNA programmable riboswitch for targeting adverse cardiac remodeling.,40861898,PMC12375242,10.1016/j.omtn.2025.102667,https://pubmed.ncbi.nlm.nih.gov/40861898/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Unexpectedly, the 2nd generation Cond-siRNA also appeared to decrease NFATc1 levels in the PBS group (independent of its effect on PPP3CA), suggesting an off-target effect or a cellular stress response to this chemical entity.",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,483,SMILR siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Transcriptomic analyses of BHF7-transfected vSMCs demonstrates expected changes to known SMILR regulated genes without apparent toxic effect; paragraph 43,8415,Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure.,40928446,PMC12790151,10.1016/j.jacbts.2025.101364,https://pubmed.ncbi.nlm.nih.gov/40928446/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Grade adjusted A->B: PMID 40928446; pmc_full_text evidence was direct but less than full primary-detail confidence for seed-mediated off-target effect.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,493,PH-762,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,transcriptome-level off-target effect,transcriptome-level off-target effect,B,Results > PH-762 is a stabilized self-delivering siRNA compound designed to potently silence PDCD1 mRNA with high specificity; paragraph 10,10539,Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy.,39697325,PMC11652358,10.3389/fimmu.2024.1501679,https://pubmed.ncbi.nlm.nih.gov/39697325/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"The in silico predictions were confirmed experimentally in CD3/CD28 bead-activated human pan T cells, where no off-target silencing GRAMD4 mRNA was observed, such that an IC50 for PH-762 toward GRAMD4 mRNA could not be determined",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,506,siIGF1R-1,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > Transcriptomics and proteomics analysis of modified CT102s; paragraph 23,14112,Modified ASO conjugates encapsulated with cytidinyl/cationic lipids exhibit more potent and longer-lasting anti-HCC effects.,37251692,PMC10220282,10.1016/j.omtn.2023.04.028,https://pubmed.ncbi.nlm.nih.gov/37251692/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"It was found that modified CT102s could decrease IGF1R mRNA expression levels in both the nucleus and cytoplasm (Figure 6F) and had a significant effect on the expression of GAS2 (GenBank: NM_001143830), POLA2 (GenBank: NM_002689), LGALS2 (GenBank: NM_006498), and IGFBP1 (GenBank: NM_000596), which have functional roles in the occurrence and development of tumors, possibly by imperfect base pairing",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,510,SLN360,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,RESULTS > SLN360 Specifically Downregulates LPA in Primary Hepatocytes; paragraph 28,1486,"Preclinical Toxicological Assessment of A Novel siRNA, SLN360, Targeting Elevated Lipoprotein (a) in Cardiovascular Disease.",35737426,PMC9516055,10.1093/toxsci/kfac067,https://pubmed.ncbi.nlm.nih.gov/35737426/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Except for the pseudogene LPAL2, none of the other identified potential off targets, nor PLG, showed any concentration-dependent reduction in mRNA expression up to SLN360 concentrations of 1000 nM, over 300-fold the IC50 for SLN360 in primary human hepatocytes",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,526,HTT siRNA,siRNA,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target effect,seed-mediated off-target effect,B,Results > Di-siRNA modulates HTT expression with minimal off-target events; paragraph 33,4213,A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.,31375812,PMC6879195manuscript-id: NIHMS1533065,10.1038/s41587-019-0205-0,https://pubmed.ncbi.nlm.nih.gov/31375812/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Thus, there were only two potential genes, APOLD1 (~ 40% down) and ANLN (~ 20% down), that may be down-regulated due to miRNA-like off-target silencing",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,530,CEP290; LCA10,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,"Results > QR-110 Treatment Reduces Aberrant Splicing, Increases Wild-Type CEP290 in Homozygous Retinal Organoids, and Shows No Off-Target Pharmacology; paragraph 15",12621,Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.,30114557,PMC6092551,10.1016/j.omtn.2018.07.010,https://pubmed.ncbi.nlm.nih.gov/30114557/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,"Using a 2-fold change as a cutoff, 44 differentially expressed genes were identified, but none has complementarity to QR-110 (Table S8)",2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,534,89E-06,ASO,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,hybridization/mismatch off-target effect,hybridization/mismatch off-target effect,B,Results > High Confirmation Rate of In Silico Predicted OTEs in Mouse Liver; paragraph 14,2064,Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs.,28918038,PMC5537172,10.1016/j.omtn.2017.07.003,https://pubmed.ncbi.nlm.nih.gov/28918038/,abstract_metadata_only,derived_annotations_only,source-localized derived annotation,false,1,0,curator_verified,accept,ni_jie,Our data show that liver toxicity of LNA-containing gapmer ASOs is associated with their ability to hybridize to off-target transcripts and downregulate their expression.,2026-06-07T02:20:35+00:00
offtarget,offtarget_evidence,535,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-based off-target suppression,seed-based off-target suppression,B,PMC full text high-precision preselection,12077,Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.,39231537,PMC11472056,10.1093/nar/gkae741,https://pubmed.ncbi.nlm.nih.gov/39231537/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""All gates pass: siRNA modification is tested and observed to suppress seed-region off-target activity."", ""grounding_quote"": ""the siRNAs with different sequences incorporating 2′-formamidonucleoside with four kinds of nucleobases into any position other than 2nd position in the seed region revealed a significant suppression of off-target activity while maintaining on-target RNAi activity"", ""source_pmid"": ""39231537"", ""candidate_domain"": ""offtarget""}",2026-06-07T21:51:24.363916+00:00
offtarget,offtarget_evidence,536,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,unexpected cGAS signaling suppression,unexpected cGAS signaling suppression,B,PMC full text high-precision preselection,2281,An off-target effect of class A CpG-oligonucleotides on suppressing the cyclic GMP-AMP synthase signaling in fibroblastic reticular cells.,40337520,PMC12055788,10.3389/fphar.2025.1576151,https://pubmed.ncbi.nlm.nih.gov/40337520/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""All gates pass: therapeutic CpG oligonucleotides show an observed unintended suppression of cGAS signaling."", ""grounding_quote"": ""Unexpectedly, we found that class A ODNs suppress the cGAS level and downstream signaling in human and murine FRC."", ""source_pmid"": ""40337520"", ""candidate_domain"": ""offtarget""}",2026-06-07T21:51:24.364917+00:00
offtarget,offtarget_evidence,537,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,seed-mediated off-target,seed-mediated off-target,B,PMC full text high-precision preselection,2308,The siRNA Off-Target Effect Is Determined by Base-Pairing Stabilities of Two Different Regions with Opposite Effects.,35205363,PMC8872465,10.3390/genes13020319,https://pubmed.ncbi.nlm.nih.gov/35205363/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""All gates pass: the passage reports seed-mediated siRNA suppression of unintended mRNAs."", ""grounding_quote"": ""siRNA also suppresses the expression of unintended mRNAs with partially complementary sequences mainly within the siRNA seed region"", ""source_pmid"": ""35205363"", ""candidate_domain"": ""offtarget""}",2026-06-07T21:51:24.366422+00:00
offtarget,offtarget_evidence,538,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,minimal off-target activity,minimal off-target activity,B,PMC full text high-precision preselection,4173,DUX4 Transcript Knockdown with Antisense 2'-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy.,33068777,PMC7854280,10.1016/j.ymthe.2020.10.010,https://pubmed.ncbi.nlm.nih.gov/33068777/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,zy,"{""reason"": ""All gates pass: antisense 2'-MOE gapmers were experimentally assessed and showed minimal off-target activity."", ""grounding_quote"": ""Using immortalized patient-derived muscle cells and local intramuscular injections in the FLExDUX4 FSHD mouse model, we showed that our designed 2′-MOE gapmers significantly reduced DUX4 transcript levels in vitro and in vivo, respectively. Furthermore, in vitro, we observed significantly reduced expression of DUX4-activated downstream targets, restoration of FSHD signature genes by RNA sequencing, significant improvements in myotube morphology, and minimal off-target activity."", ""source_pmid"": ""33068777"", ""candidate_domain"": ""offtarget""}",2026-06-07T21:51:24.371957+00:00
offtarget,offtarget_evidence,539,unspecified oligonucleotide,ASO/siRNA mixed context,,,,,,,,,,,,needs_curator_sequence_curation,needs_curator_modification_curation,TLR3-mediated off-target immune activation,TLR3-mediated off-target immune activation,C,PMC full text high-precision preselection,4056,A β-Cyclodextrin-Based Nanoparticle with Very High Transfection Efficiency Unveils siRNA-Activated TLR3 Responses in Human Prostate Cancer Cells.,36365241,PMC9692777,10.3390/pharmaceutics14112424,https://pubmed.ncbi.nlm.nih.gov/36365241/,abstract_metadata_only,derived_annotations_only,source-linked derived annotation,false,1,0,curator_verified,accept,sm,"{""reason"": ""Observed scramble-siRNA effect indicates an unintended siRNA off-target response; generic cell-line support so Grade C."", ""grounding_quote"": ""We found that double knockdown of p42-MAPK and Rheb increased DTX-toxicity in LNCaP but not in PC3 cells. However, we also observed the same effect when scramble siRNA was used, therefore pointing to an off-target effect."", ""source_pmid"": ""36365241"", ""candidate_domain"": ""offtarget""}",2026-06-07T21:51:24.377467+00:00