{ "version": "20260604_core_validation_v45", "input": { "raw_sequence": "AUGCUACUGACUGA", "canonical_dna_sequence": "ATGCTACTGACTGA", "length": 14, "target": "PCSK9", "modification": "GalNAc", "endpoint": "" }, "sequence_features": { "seed_2_8": "TGCTACT", "unique_7mer_windows_first_12": [ "ATGCTAC", "TGCTACT", "GCTACTG", "CTACTGA", "TACTGAC", "ACTGACT", "CTGACTG", "TGACTGA" ], "contains_ambiguous_base": false }, "status": { "release_grade_sequence_columns_available": true, "release_grade_sequence_alignment_available": false, "current_mode": "sequence parsing plus seed/off-target/modification evidence lookup", "upgrade_needed": "Curate release-grade oligo sequence and modification strings before claiming full sequence-alignment search.", "sequence_coverage_endpoint": "/api/sequence_coverage", "curation_template": "/api/download/sequence_modification_curation_template.csv" }, "evidence_query": { "terms": [ "PCSK9", "GalNAc", "seed", "off-target", "hybridization", "mismatch" ], "release_endpoint": "/api/evidence_records?q=PCSK9+GalNAc+seed+off-target&limit=25&target=PCSK9", "candidate_endpoint": "/api/curation_candidates?q=GalNAc&limit=25" }, "release_hits": [ { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 48, "canonical_name": "HsPCSK9-1811-LNA/GalNAc ASO panel from PMID 34760338", "modality": "ASO", "target_gene_symbol": "PCSK9", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "renal; hepatic", "evidence_label": "renal and hepatic safety", "evidence_grade": "A", "source_location": "Results > Evaluating the safety of the GalNAc conjugate in rat; paragraph 15", "source_document_id": 1632, "source_title": "Drug discovery and development scheme for liver-targeting bridged nucleic acid antisense oligonucleotides.", "pmid": "34760338", "source_pmcid": "PMC8560717", "doi": "10.1016/j.omtn.2021.10.008", "source_url": "https://pubmed.ncbi.nlm.nih.gov/34760338/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "Histopathological examination revealed mild injury with degeneration, karyomegaly, single-cell necrosis, and vacuolation in proximal tubules in both animals dosed at 30 mg/kg.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 250, "canonical_name": "PCSK9; Inclisiran", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "safety/tolerability", "evidence_grade": "B", "source_location": "PubMed abstract", "source_document_id": 1217, "source_title": "Muscle Adverse Events Associated With Inclisiran: Data Mining of FAERS Database and Mendelian Randomization Analysis.", "pmid": "41289434", "source_pmcid": null, "doi": "10.1097/FJC.0000000000001778", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41289434/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "Among 4685 adverse event reports of inclisiran, 523 MAEs reports were found.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 313, "canonical_name": "PCSK9; GN3; MC3-LNP", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "C", "source_location": "PubMed abstract", "source_document_id": 11712, "source_title": "Engineering a biomimetic system for hepatocyte-specific RNAi treatment of non-alcoholic fatty liver disease.", "pmid": "37951519", "source_pmcid": null, "doi": "10.1016/j.actbio.2023.10.038", "source_url": "https://pubmed.ncbi.nlm.nih.gov/37951519/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 359, "canonical_name": "PCSK9; NCT04652726; inclisiran", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "B", "source_location": "PubMed abstract", "source_document_id": 1155, "source_title": "Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial.", "pmid": "41616799", "source_pmcid": null, "doi": "10.1016/S2213-8587(25)00351-1", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41616799/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "Inclisiran was well tolerated, with a safety profile comparable to studies in adults.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 361, "canonical_name": "PCSK9; inclisiran", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "B", "source_location": "PubMed abstract", "source_document_id": 1179, "source_title": "Comparative effectiveness and safety of inclisiran versus evolocumab and alirocumab: a 180-day real-world study.", "pmid": "42141407", "source_pmcid": null, "doi": "10.1186/s12872-026-05931-5", "source_url": "https://pubmed.ncbi.nlm.nih.gov/42141407/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "All therapies were well-tolerated with no new safety signals.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 382, "canonical_name": "PCSK9; NCT05763875; Inclisiran", "modality": "ASO/siRNA mixed context", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "B", "source_location": "PubMed abstract", "source_document_id": 2280, "source_title": "Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial.", "pmid": "40392667", "source_pmcid": null, "doi": "10.1016/j.jacc.2025.04.049", "source_url": "https://pubmed.ncbi.nlm.nih.gov/40392667/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "Inclisiran was well tolerated, with no new safety concerns.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 401, "canonical_name": "PCSK9; NCT03060577; inclisiran", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "B", "source_location": "PubMed abstract", "source_document_id": 2697, "source_title": "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.", "pmid": "36620965", "source_pmcid": null, "doi": "10.1016/S2213-8587(22)00353-9", "source_url": "https://pubmed.ncbi.nlm.nih.gov/36620965/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-linked derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 414, "canonical_name": "Inclisiran", "modality": "siRNA", "target_gene_symbol": "PCSK9", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "clinical laboratory safety", "evidence_grade": "A", "source_location": "RESULTS > Safety Analysis; paragraph 36", "source_document_id": 2498, "source_title": "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.", "pmid": "40391436", "source_pmcid": "PMC12180692", "doi": "10.1161/CIRCULATIONAHA.124.073233", "source_url": "https://pubmed.ncbi.nlm.nih.gov/40391436/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 417, "canonical_name": "Inclisiran", "modality": "siRNA", "target_gene_symbol": "PCSK9", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "treatment-emergent adverse events", "evidence_grade": "A", "source_location": "Results > Safety; paragraph 23", "source_document_id": 2632, "source_title": "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.", "pmid": "36550348", "source_pmcid": "PMC11101568", "doi": "10.1007/s10557-022-07413-0", "source_url": "https://pubmed.ncbi.nlm.nih.gov/36550348/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 420, "canonical_name": "G5-GalNAc siRNA platform", "modality": "siRNA", "target_gene_symbol": "PCSK9/AGT", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "nonclinical toxicology and biodistribution safety", "evidence_grade": "C", "source_location": "Discussion; paragraph 17", "source_document_id": 1069, "source_title": "Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.", "pmid": "41541269", "source_pmcid": "PMC12800395", "doi": "10.1016/j.omtn.2025.102801", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41541269/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "The no observed adverse effect level was established at 300 mg/kg.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 556, "canonical_name": "siPCSK9 (recovered B2 from PMID:41290746, curator:CM)", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "unspecified", "modification_annotation_status": "unspecified", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "A", "source_location": "Results > NP containing PCSK9 siRNA and STING agonists enable safe and effective cancer immunotherapy; paragraph 17", "source_document_id": 7717, "source_title": "Silencing PCSK9 reshapes the spatiotemporal activation of STING for safe and effective cancer immunotherapy.", "pmid": "41290746", "source_pmcid": "PMC12749358", "doi": "10.1038/s41467-025-66630-x", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41290746/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "exhibited excellent safety profiles, without body weight changes at 24 h and 48 h post-administration", "audited_at": "2026-06-07T02:20:35+00:00" } ], "candidate_hits": [ { "id": 16, "queue_id": 30, "pmid": "37589246", "doi": "10.1002/jcph.2337", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 5", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: Pharmacokinetics and Pharmacodynamics of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Pharmacokinetics and Pharmacodynamics of GalNAc-Conjugated siRNAs." }, { "id": 17, "queue_id": 31, "pmid": "37589246", "doi": "10.1002/jcph.2337", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 5", "matched_terms": "galnac;conjugated", "candidate_signal": "delivery candidate; matched derived terms: galnac, conjugated; source title: Pharmacokinetics and Pharmacodynamics of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Pharmacokinetics and Pharmacodynamics of GalNAc-Conjugated siRNAs." }, { "id": 20, "queue_id": 38, "pmid": "38334488", "doi": "10.1097/MED.0000000000000857", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 8", "matched_terms": "galnac;conjugated", "candidate_signal": "delivery candidate; matched derived terms: galnac, conjugated; source title: APOC3 siRNA and ASO therapy for dyslipidemia.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "APOC3 siRNA and ASO therapy for dyslipidemia." }, { "id": 24, "queue_id": 52, "pmid": "40134378", "doi": "10.1089/nat.2024.0090", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "curator_rejected", "curator_decision": "reject", "redistribution_level": "derived_annotations_only", "source_title": "Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates." }, { "id": 25, "queue_id": 53, "pmid": "40134378", "doi": "10.1089/nat.2024.0090", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;conjugated", "candidate_signal": "delivery candidate; matched derived terms: galnac, conjugated; source title: Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates." }, { "id": 26, "queue_id": 54, "pmid": "40134378", "doi": "10.1089/nat.2024.0090", "evidence_domain": "offtarget", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 2", "matched_terms": "off-target;seed;silencing", "candidate_signal": "offtarget candidate; matched derived terms: off-target, seed, silencing; source title: Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "machine_precurated_v1", "curator_decision": "accept", "redistribution_level": "derived_annotations_only", "source_title": "Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates." }, { "id": 50, "queue_id": 116, "pmid": "41021771", "doi": "10.1111/cts.70344", "evidence_domain": "toxicity", "candidate_modality": "ASO", "source_location": "PubMed abstract sentence 2", "matched_terms": "safety;tolerability", "candidate_signal": "toxicity candidate; matched derived terms: safety, tolerability; source title: Pharmacokinetics and Safety of Pelacarsen, a GalNAc(3)-Conjugated Antisense Oligonucleotide Targeting Apo(a), in Participants With Mild Hepatic Impairment.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "machine_precurated_v1", "curator_decision": "accept", "redistribution_level": "derived_annotations_only", "source_title": "Pharmacokinetics and Safety of Pelacarsen, a GalNAc(3)-Conjugated Antisense Oligonucleotide Targeting Apo(a), in Participants With Mild Hepatic Impairment." }, { "id": 51, "queue_id": 119, "pmid": "41994868", "doi": "10.1093/nar/gkag345", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 2", "matched_terms": "modified;galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: modified, galnac, lna, conjugate; source title: Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency." }, { "id": 70, "queue_id": 160, "pmid": "42070763", "doi": "10.1016/j.ejphar.2026.178917", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 4", "matched_terms": "modified;galnac;lna", "candidate_signal": "chemistry candidate; matched derived terms: modified, galnac, lna; source title: Targeted knockdown of hepatic XDH via GalNAc-siRNA alleviates hyperuricaemia and renal injury in UOX(-/-) mice.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Targeted knockdown of hepatic XDH via GalNAc-siRNA alleviates hyperuricaemia and renal injury in UOX(-/-) mice." }, { "id": 84, "queue_id": 188, "pmid": "40151235", "doi": "10.1021/jacsau.5c00012", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 3", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: 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.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "curator_verified", "curator_decision": "accept", "redistribution_level": "derived_annotations_only", "source_title": "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." }, { "id": 90, "queue_id": 202, "pmid": "42149053", "doi": "10.1039/d6tb00003g", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 5", "matched_terms": "modified;galnac;lna", "candidate_signal": "chemistry candidate; matched derived terms: modified, galnac, lna; source title: GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting." }, { "id": 91, "queue_id": 203, "pmid": "42149053", "doi": "10.1039/d6tb00003g", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 4", "matched_terms": "delivery;nanoparticle;lnp", "candidate_signal": "delivery candidate; matched derived terms: delivery, nanoparticle, lnp; source title: GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting." }, { "id": 92, "queue_id": 204, "pmid": "42149053", "doi": "10.1039/d6tb00003g", "evidence_domain": "toxicity", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 11", "matched_terms": "safety;hematological", "candidate_signal": "toxicity candidate; matched derived terms: safety, hematological; source title: GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "curator_rejected", "curator_decision": "reject", "redistribution_level": "derived_annotations_only", "source_title": "GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting." }, { "id": 93, "queue_id": 207, "pmid": "42112102", "doi": "10.1016/j.omtn.2026.102936", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics." }, { "id": 94, "queue_id": 208, "pmid": "42112102", "doi": "10.1016/j.omtn.2026.102936", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;conjugated", "candidate_signal": "delivery candidate; matched derived terms: galnac, conjugated; source title: A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics." }, { "id": 100, "queue_id": 224, "pmid": "41949334", "doi": "10.1111/cts.70536", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 4", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs." }, { "id": 101, "queue_id": 225, "pmid": "41949334", "doi": "10.1111/cts.70536", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 4", "matched_terms": "galnac;conjugated;uptake", "candidate_signal": "delivery candidate; matched derived terms: galnac, conjugated, uptake; source title: A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs." }, { "id": 102, "queue_id": 226, "pmid": "41949334", "doi": "10.1111/cts.70536", "evidence_domain": "assay", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 11", "matched_terms": "screen;preclinical;model", "candidate_signal": "assay candidate; matched derived terms: screen, preclinical, model; source title: A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs." }, { "id": 103, "queue_id": 227, "pmid": "41949334", "doi": "10.1111/cts.70536", "evidence_domain": "toxicity", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 9", "matched_terms": "toxicity;toxic;hepatotoxicity", "candidate_signal": "toxicity candidate; matched derived terms: toxicity, toxic, hepatotoxicity; source title: A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "machine_precurated_v1", "curator_decision": "accept", "redistribution_level": "derived_annotations_only", "source_title": "A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs." }, { "id": 118, "queue_id": 262, "pmid": "41541269", "doi": "10.1016/j.omtn.2025.102801", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; source title: Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing." }, { "id": 119, "queue_id": 263, "pmid": "41541269", "doi": "10.1016/j.omtn.2025.102801", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 2", "matched_terms": "delivery;galnac;conjugated", "candidate_signal": "delivery candidate; matched derived terms: delivery, galnac, conjugated; source title: Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing." }, { "id": 122, "queue_id": 270, "pmid": "41388232", "doi": "10.1007/s40262-025-01606-0", "evidence_domain": "chemistry", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "chemical;galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: chemical, galnac, lna, conjugate; source title: Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.", "suggested_evidence_grade": "B", "confidence_label": "high_candidate", "validation_status": "candidate_needs_curator_review", "curator_decision": "pending", "redistribution_level": "derived_annotations_only", "source_title": "Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules." }, { "id": 123, "queue_id": 271, "pmid": "41388232", "doi": "10.1007/s40262-025-01606-0", "evidence_domain": "delivery", "candidate_modality": "siRNA", "source_location": "PubMed abstract sentence 1", "matched_terms": "galnac;conjugated", "candidate_signal": "delivery candidate; 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matched derived terms: galnac, conjugated; source title: Whole-Body Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling for Interspecies Translation and Mechanistic Characterization of Plasma and Tissue Disposition of GalNAc-siRNAs.", "suggested_evidence_grade": "C", "confidence_label": "high_candidate", "validation_status": "curator_rejected", "curator_decision": "reject", "redistribution_level": "derived_annotations_only", "source_title": "Whole-Body Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling for Interspecies Translation and Mechanistic Characterization of Plasma and Tissue Disposition of GalNAc-siRNAs." } ], "modification_profiles": [ { "term": "galnac", "label": "GalNAc conjugation", "kind": "targeted conjugate", "synonyms": [ "galnac", "n-acetylgalactosamine" ], "release_records": 33, "candidate_records": 307, "benchmark_records": 16, "domain_counts": [ { "domain": "offtarget", "n": 8 }, { "domain": "toxicity", "n": 25 } ], "grade_counts": [ { "grade": "A", "n": 10 }, { "grade": "B", "n": 15 }, { "grade": "C", "n": 8 } ], "example_release_records": [ { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 16, "canonical_name": "JNJ-3989/JNJ-73763989 GalNAc-siRNA regimen from PMID 40919077", "modality": "siRNA", "target_gene_symbol": "HBV", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "safety/tolerability", "evidence_grade": "B", "source_location": "Results > Safety; paragraph 22", "source_document_id": 3517, "source_title": "Peginterferon-alpha-2a add-on to treatment with siRNA JNJ-73763989 in virologically suppressed chronic hepatitis B: The phase II PENGUIN study.", "pmid": "40919077", "source_pmcid": "PMC12409438", "doi": "10.1016/j.jhepr.2025.101516", "source_url": "https://pubmed.ncbi.nlm.nih.gov/40919077/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 40, "canonical_name": "ESC+ GalNAc-siRNA D1/D4/D6/D9 panel from PMID 35736224", "modality": "siRNA", "target_gene_symbol": "TTR; HAO1", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "A", "source_location": "RESULTS > GNA improves the therapeutic index in rats; paragraph 33", "source_document_id": 1411, "source_title": "From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization.", "pmid": "35736224", "source_pmcid": "PMC9262600", "doi": "10.1093/nar/gkac539", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35736224/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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).", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 45, "canonical_name": "GalNAc-G-quadruplex oligonucleotide panel from PMID 35745067", "modality": "ASO", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "general safety", "evidence_label": "cytotoxicity", "evidence_grade": "C", "source_location": "2. Results > 2.4. Toxicity Assays; paragraph 17", "source_document_id": 4073, "source_title": "Properties of Parallel Tetramolecular G-Quadruplex Carrying N-Acetylgalactosamine as Potential Enhancer for Oligonucleotide Delivery to Hepatocytes.", "pmid": "35745067", "source_pmcid": "PMC9228010", "doi": "10.3390/molecules27123944", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35745067/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 48, "canonical_name": "HsPCSK9-1811-LNA/GalNAc ASO panel from PMID 34760338", "modality": "ASO", "target_gene_symbol": "PCSK9", "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "renal; hepatic", "evidence_label": "renal and hepatic safety", "evidence_grade": "A", "source_location": "Results > Evaluating the safety of the GalNAc conjugate in rat; paragraph 15", "source_document_id": 1632, "source_title": "Drug discovery and development scheme for liver-targeting bridged nucleic acid antisense oligonucleotides.", "pmid": "34760338", "source_pmcid": "PMC8560717", "doi": "10.1016/j.omtn.2021.10.008", "source_url": "https://pubmed.ncbi.nlm.nih.gov/34760338/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "Histopathological examination revealed mild injury with degeneration, karyomegaly, single-cell necrosis, and vacuolation in proximal tubules in both animals dosed at 30 mg/kg.", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 59, "canonical_name": "GalNAc AON-B/D/E panel from PMID 30583097", "modality": "ASO", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "renal", "evidence_label": "renal safety", "evidence_grade": "A", "source_location": "Results > GalNAc Conjugation Masked the In Vivo Nephrotoxicity Potential of AON Drug Candidates; paragraph 7", "source_document_id": 2059, "source_title": "GalNAc Conjugation Attenuates the Cytotoxicity of Antisense Oligonucleotide Drugs in Renal Tubular Cells.", "pmid": "30583097", "source_pmcid": "PMC6305803", "doi": "10.1016/j.omtn.2018.11.005", "source_url": "https://pubmed.ncbi.nlm.nih.gov/30583097/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "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).", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 60, "canonical_name": "GalNAc-siRNA hepatotoxicity panel with REVERSIR from PMID 29459660", "modality": "siRNA", "target_gene_symbol": "HAO1; 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paragraph 42", "source_document_id": 1242, "source_title": "Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases.", "pmid": "40692538", "source_pmcid": "PMC12277184", "doi": "10.2147/IJN.S510937", "source_url": "https://pubmed.ncbi.nlm.nih.gov/40692538/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "No significant toxicity was observed in vital organs (ALT/AST levels, P>0.05; histopathology scores, P>0.05).", "audited_at": "2026-06-07T02:20:35+00:00" }, { "evidence_domain": "toxicity", "entity_table": "toxicity_endpoint", "evidence_id": 117, "canonical_name": "siRNA candidate from PMID 41949334", "modality": "siRNA", "target_gene_symbol": null, "disease_context": null, "sense_sequence": null, "antisense_sequence": null, "guide_sequence": null, "passenger_sequence": null, "seed_region": null, "backbone_chemistry": null, "sugar_modification": null, "base_modification": null, "conjugate_delivery": null, "sequence_annotation_status": "needs_curator_sequence_curation", "modification_annotation_status": "needs_curator_modification_curation", "category": "hepatic", "evidence_label": "hepatotoxicity", "evidence_grade": "B", "source_location": "Results > Treatment of Hepatic Spheroids With Chemically Modified GalNAc‐Conjugated siRNA; FIGURE 2 caption", "source_document_id": 1059, "source_title": "A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.", "pmid": "41949334", "source_pmcid": "PMC13059674", "doi": "10.1111/cts.70536", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41949334/", "source_license_status": "abstract_metadata_only", "source_reuse_category": "derived_annotations_only", "curation_basis": "source-localized derived annotation", "raw_quote_included": "false", "is_observed_experimental": 1, "is_computational_prediction": 0, "audit_validation_status": "curator_verified", "curator_decision": "accept", "curator_id": "ni_jie", "audit_note": "No signs of hepatotoxicity were observed under the conditions used.", "audited_at": "2026-06-07T02:20:35+00:00" } ], "example_candidates": [ { "id": 16, "evidence_domain": "chemistry", "candidate_modality": "siRNA", "matched_terms": "galnac;lna;conjugate", "candidate_signal": "chemistry candidate; matched derived terms: galnac, lna, conjugate; 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