gap_addressed,hepatotoxicity_relevance,judging_criterion,modality_focus,source_id,source_role,source_title,source_year,triage_tier,use_in_core_dataset,value_origin
"supporting delivery, mechanism, disease, or assay context that improves model realism",governing,Potential Impact,ASO|gapmer|siRNA|GalNAc-siRNA,MEMO_OLIGOTOX_PHASE2_ALIGNMENT,governing_schema_and_rules,DBbun OligoTox Phase 2 Alignment Memo,2026,supporting,yes,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_genetics_MASLD_precision_therapy_context,Potential Impact,siRNA|ASO,PNPLA3_ROMEO_VALENTI_2025,PNPLA3_precision_genetics_siRNA_ASO_therapeutic_targeting_context,Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics,2025,supporting,supporting,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_clinical_low_DILI_GalNAc_siRNA_liver_safety_and_hepatocyte_target_knockdown_reference,Potential Impact,GalNAc-siRNA|HSD17B13|rapirosiran|MASH|ALT|AST|NAS|liver_biopsy|ASGPR,RAPIROSIRAN_SANYAL_2025,HSD17B13_GalNAc_siRNA_clinical_PK_PD_liver_safety_and_MASH_histology_context,Phase I randomized double-blind study of an RNA interference therapeutic targeting HSD17B13 for metabolic dysfunction-associated steatohepatitis,2025,direct,yes_core_clinical_PK_PD_safety_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",human_liver_model_and_no_observed_toxicity_context,Potential Impact,GalNAc-siRNA,LIVER_SPHEROID_SCHOLTEN_2026,human_liver_spheroid_GalNAc_siRNA_screening,A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs,2026,supporting,yes,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",clinical_transaminase_and_narrow_window_context,Potential Impact,GalNAc-LNA-ASO,RO7239958_GERETTI_2025,ASO_safety_PK_PD_transaminase_reference,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",2025,supporting,yes,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",delivery_related_hepatic_targeting_immunogenicity_and_nanocarrier_toxicity_context,Potential Impact,siRNA|ASO|RNAi|nanocarrier_delivery,MOHAMED_NANOPARTICLE_HEPATITIS_2026,nanoparticle_delivery_hepatic_targeting_and_safety_context,Nanoparticle approaches for hepatitis therapy and clinical translation,2026,supporting,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_delivery_payload_and_immune_activation_context_not_direct_oligotox_hepatotoxicity,Potential Impact,siRNA|mRNA|hybrid_RNA_LNP|PCSK9_siRNA,MENG_HYBRID_RNA_LNP_HCC_2025,hybrid_RNA_LNP_payload_architecture_and_liver_tumour_immunomodulation_context,Reversal of tumour immune evasion via enhanced MHC-Class-I antigen presentation by a dual-functional RNA regulated system,2025,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_lipid_homeostasis_and_APOB_ASO_context_not_direct_hepatotoxicity,Potential Impact,ASO|Mipomersen|APOB|MTTP|VLDL_secretion,CHEN_OVARIAN_MTTP_APOB_MIPOMERSEN_2025,APOB_ASO_mipomersen_lipid_export_and_lipotoxic_stress_context,Ovarian expression of functional MTTP and apoB for VLDL assembly and secretion in chickens,2025,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_liver_disease_lipid_accumulation_and_siRNA_knockdown_context_not_direct_oligotox_toxicity,Potential Impact,siRNA|SULT1B1|CEBPB|hepatocyte_lipid_accumulation|H3K27ac|JQ1,LU_SULT1B1_SE_MASLD_2026,MASLD_epigenetic_lipid_accumulation_SULT1B1_CEBPB_siRNA_context,Super-enhancer-driven recruitment of C/EBPbeta by SULT1B1 is implicated in metabolic dysfunction-associated steatotic liver disease progression,2026,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_platform_specific_liver_safety_signal_for_ANGPTL3_oligonucleotides,Potential Impact,GalNAc-ASO|GalNAc-siRNA|ANGPTL3|vupanorsen|ARO-ANG3|ALT_AST|hepatic_fat_fraction,OOSTVEEN_ANGPTL3_LIVER_SAFETY_2023,ANGPTL3_ASO_vs_siRNA_liver_safety_and_hepatic_fat_context,Angiopoietin-like 3 inhibition and the liver: less is more?,2023,direct,yes_supporting_direct_liver_safety_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_extrahepatic_delivery_and_systemic_tolerability_context_not_direct_hepatotoxicity,Potential Impact,cholesterol-conjugated_siRNA|ALK4|skeletal_muscle|mdx_mouse|extrahepatic_delivery,ENGELBEEN_ALK4_MUSCLE_SIRNA_2023,cholesterol_conjugated_siRNA_extrahepatic_delivery_tolerability_context,Efficient Downregulation of Alk4 in Skeletal Muscle After Systemic Treatment with Conjugated siRNAs in a Mouse Model for Duchenne Muscular Dystrophy,2023,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_ASO_design_and_safety_workflow_context_not_direct_hepatotoxicity,Potential Impact,splice-switching_ASO|2prime-MOE|phosphorothioate|intrathecal|offtarget_screen|N-of-1,KIM_MILASEN_CUSTOM_ASO_2019,patient_customized_splice_modulating_ASO_design_safety_workflow_context,Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease,2019,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_review_context_for_ASO_liver_uptake_hepatic_injury_offtarget_sequence_motifs_and_metabolic_NAFLD_targets,Potential Impact,ASO|gapmer|GalNAc-ASO|NAFLD|obesity|DNL|RNase_H1|hepatotoxicity|offtarget|IFN_response,KEATING_ASO_OBESITY_NAFLD_2022,ASO_metabolic_NAFLD_targeting_delivery_chemistry_and_hepatotoxicity_challenges_context,Antisense Oligonucleotide Technologies to Combat Obesity and Fatty Liver Disease,2022,direct,yes_supporting_ASO_metabolic_safety_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_sequence_and_modification_based_hepatotoxicity_prediction_for_therapeutic_oligonucleotides,Potential Impact,LNA_gapmer|phosphorothioate_ASO|RNase_H|sequence_motif|ALT|histopathology|random_forest_classifier,HAGEDORN_LNA_HEPATOTOX_RF_2013,sequence_modification_pattern_hepatotoxicity_prediction_context,Hepatotoxic Potential of Therapeutic Oligonucleotides Can Be Predicted from Their Sequence and Modification Pattern,2013,direct,yes_sequence_modification_toxicity_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_siRNA_sequence_modification_safety_and_clinical_ALT_context,Potential Impact,GalNAc-siRNA|ESCplus|glycol_nucleic_acid|seed_region|HBV_X|ALT|HBsAg,GANE_VIR2218_ALNHBV_HBV_RNAI_2023,GalNAc_siRNA_ESCplus_seed_region_offtarget_and_ALT_safety_context,Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials,2023,direct,yes_supporting_RNAi_sequence_safety_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_clinical_GalNAc_siRNA_hepatocyte_targeting_and_systemic_safety_monitoring_context_not_direct_hepatotoxicity,Potential Impact,GalNAc-siRNA|AGT|angiotensinogen|RAAS|hypertension|ASGPR|RISC|endosomal_depot,DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,zilebesiran_GalNAc_siRNA_AGT_RAAS_blood_pressure_durability_and_safety_monitoring_context,Zilebesiran—Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension,2025,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_offtarget_design_context_not_direct_hepatotoxicity,Potential Impact,siRNA|GalNAc-siRNA|modified_siRNA|guide_strand_bulge|off_target_prediction,HAUPTMANN_SIRNA_BULGES_GALNAC_2022,guide_strand_bulge_tolerance_GalNAc_siRNA_offtarget_prediction_context,Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression,2022,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_liver_cancer_malignant_state_and_siRNA_design_context_not_direct_oligonucleotide_hepatotoxicity,Potential Impact,research_siRNA|FBLL1|HCC|spatial_transcriptomics|single_cell_RNAseq|EGFR_MAPK|c_Myc|hepatocyte_dedifferentiation,XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,FBLL1_HCC_malignant_hepatocyte_spatial_context_and_siRNA_knockdown_growth_suppression_context,Integrated Multi-Omics and Spatial Transcriptomics Identify FBLL1 as a Malignant Transformation Driver in Hepatocellular Carcinoma,2026,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_hepatocyte_delivery_biocompatibility_liver_injury_regeneration_and_function_recovery_context_not_direct_oligotox_hepatotoxicity,Potential Impact,GalNAc-LNP-siRNA|siMKK4|MKK4|ASGPR|hepatocyte_targeting|liver_regeneration|ACLF,ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,GalNAc_modified_LNP_siMKK4_hepatocyte_targeting_liver_regeneration_ACLF_context,Dual targeted gene delivery strategy mediated by GalNAc-modified lipid nanoparticles enhances liver regeneration through specific knockdown of MKK4,2026,direct,supporting_delivery_and_liver_regeneration_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_liver_microenvironment_ALT_AST_MASLD_progression_context_not_direct_oligo_toxicity,Potential Impact,hepatocyte_derived_sEV|OGT|LSEC|MASLD|Ang-2|BAGN,WANG_OGT_SEV_LSEC_MASLD_2026,MASLD_LSEC_capillarization_extracellular_vesicle_OGT_HNF1A_Ang2_context,OGT-enriched Hepatocyte-derived Extracellular Vesicles Promote Capillarization of Liver Sinusoidal Endothelial Cells in Metabolic Dysfunction-associated Steatotic Liver Disease,2026,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_HBV_HCC_liver_disease_ASO_intervention_and_epigenetic_context_not_direct_oligotox_hepatotoxicity,Potential Impact,ASO|lncRNA|HBV_HCC|m6A_epigenetic_RNA_context,DU_MALAT1_HBV_HCC_ASO_2025,HBV_HBx_MALAT1_m6A_IGF2BP3_ASO_intervention_context,MALAT1 promotes malignancy of HBV-related hepatocellular carcinoma by regulating IGF2BP3-mediated nuclear-cytoplasmic shuttling,2025,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_MASLD_HCC_liver_disease_siRNA_therapeutic_context_not_direct_oligotox_hepatotoxicity,Potential Impact,siRNA|nanoparticle_siRNA|CD133_PROM1|sorafenib|lenvatinib|MASLD_HCC,PAN_CD133_MASLD_HCC_SIRNA_2025,MASLD_HCC_CD133_CSC_VNP_siRNA_multikinase_inhibitor_resistance_context,Targeting cancer stem cells enhances multikinase inhibitor therapy in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma,2025,direct,supporting_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_targeted_oligonucleotide_delivery_safety_ALT_AST_context,Potential Impact,GalNAc-RBC-EV|ASO|siRNA|miR-155-ASO|Rab7-siRNA|PJ34|ASGPR|hepatocyte_delivery,HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,GalNAc_RBC_EV_hepatocyte_delivery_ASO_siRNA_PJ34_ALF_NAFLD_HCC_context,Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases,2025,supporting,yes_supporting_delivery_context,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_clinical_liver_severity_and_outcome_stratification_context_not_direct_oligo_toxicity,Potential Impact,clinical-risk-score|EMR|cirrhosis|MELD-Plus|albumin|bilirubin|creatinine|INR|sodium|WBC|cholesterol|age|length-of-stay,KARTOUN_MELD_PLUS_CIRRHOSIS_2017,clinical_liver_severity_cirrhosis_mortality_risk_score_context,The MELD-Plus: A generalizable prediction risk score in cirrhosis,2017,direct,supporting_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_aldehyde_detoxification_oxidative_stress_mitochondrial_liver_context,Potential Impact,small_molecule_hepatoprotective_context_with_siRNA_validation,MA_FORMONONETIN_ALDH2_ALD_2025,supporting_liver_context,Formononetin mitigates alcoholic liver disease by restoring ALDH2 function and inducing ERK1/2–Nrf2 antioxidant signaling,2025,supporting,supporting,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_delivery_platform_safety_and_systemic_siRNA_context,Potential Impact,calcium_phosphate_hybrid_nanoparticle_siRNA,VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,supporting_delivery_platform_safety_context,In Vivo HOXB7 Gene Silencing and Cotreatment with Tamoxifen for Luminal A Breast Cancer Therapy,2024,supporting,supporting,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_sEV_RNA_loading_hepatocyte_delivery_and_systemic_safety_context,Potential Impact,engineered_small_extracellular_vesicle_siRNA_miRNA_delivery,WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,supporting_sEV_RNA_delivery_and_hepatic_safety_context,Robust loading and delivery of functional small RNAs via protein N-myristoylation-induced small extracellular vesicles,2026,supporting,supporting,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_preclinical_liver_kidney_immunotoxicity_offtarget_safety_context,Potential Impact,ASO|siRNA|miRNA_mimic|GalNAc|LNP|PS_gapmer,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,direct_preclinical_oligonucleotide_safety_framework,Preclinical Safety Assessment of Therapeutic Oligonucleotides,2022,direct,yes,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_human_liver_cancer_cell_disulfide_stress_and_noncanonical_cell_death_context_not_direct_therapeutic_oligo_hepatotoxicity,Potential Impact,IFN-alpha|HepG2|Huh7|disulfidptosis|SLC7A11_siRNA|NADPH|F-actin|D-penicillamine|B2M|USP18|PSME1,BI_IFNA_DISULFIDPTOSIS_HCC_2026,IFN_alpha_HCC_disulfidptosis_NADPH_Factin_SLC7A11_context,Interferon-alpha induces disulfidptosis occurrence in human liver cancer cells,2026,direct,supporting_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_GalNAc_siRNA_nonclinical_safety_and_liver_toxicity_platform_context,Potential Impact,GalNAc-siRNA|ESC chemistry|ASGPR|RISC|rat|cynomolgus monkey|liver|kidney|reticuloendothelial system|seed off-target hepatotoxicity,JANAS_GALNAC_RNAI_NONCLINICAL_SAFETY_2018,GalNAc_siRNA_ESC_nonclinical_safety_platform_rat_monkey_liver_kidney_RES_context,The Nonclinical Safety Profile of GalNAc-conjugated RNAi Therapeutics in Subacute Studies,2018,direct,yes_core_GalNAc_siRNA_safety_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_clinical_GalNAc_siRNA_tolerability_and_liver_enzyme_monitoring_context_not_hepatotoxicity_mechanism,Potential Impact,inclisiran|PCSK9|GalNAc-siRNA|LDL-C|LDLR|familial hypercholesterolemia|PWV|ALT|AST|CPK,BOSCO_INCLISIRAN_FH_REALWORLD_2025,inclisiran_PCSK9_GalNAc_siRNA_real_world_FH_lipid_PWV_ALT_AST_safety_context,Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience,2025,supporting,supporting_clinical_PCSK9_GalNAc_siRNA_context,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_delivery_and_safety_context_for_liver_targeted_therapeutic_oligonucleotides,Potential Impact,GalNAc|ASGPR|hepatocyte|siRNA|ASO|GalNAc-ASO|GalNAc-siRNA|endosomal_escape|ESC|ESCplus|Reversir|givosiran|inclisiran|clinical_pipeline,DEBACKER_GALNAC_LIVER_DELIVERY_REVIEW_2020,GalNAc_ASGPR_hepatocyte_delivery_ASO_siRNA_clinical_translation_and_safety_context,Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug,2020,direct,yes_core_GalNAc_liver_delivery_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_core_siRNA_pharmacology_and_liver_delivery_context_for_OligoTox_interpretation,Potential Impact,siRNA|RISC|AGO2|seed_region|GalNAc-siRNA|LNP|chemical_modification|immune_activation|off-target|approved_siRNA_drugs,RANASINGHE_SIRNA_PHARMACOLOGY_REVIEW_2023,siRNA_mechanism_pharmacology_delivery_clinical_landscape_context,"Small interfering RNA: Discovery, pharmacology and clinical development — An introductory review",2023,supporting,yes_core_siRNA_pharmacology_context,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",core_hepatotoxicity_screening_positive_negative_controls,Potential Impact,LNA_gapmer_ASO,KAMOLA_ASO_HEPATOTOX_SCREEN_2017,ASO_gapmer_hepatotoxicity_screening_offtarget_mitigation,Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs,2017,supporting,yes,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_ASO_delivery_liver_function_no_evident_hepatotoxicity_and_inflammation_context,Potential Impact,LNP-ASO|LNA_gapmer_ASO|AGO1|endothelial_cell|liver_function|ALT_AST,LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,LNP_delivered_LNA_gapmer_AGO1_ASO_liver_function_vascular_inflammation_context,Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism,2025,supporting,supporting_context_with_preprint_caution,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_systemic_ASO_tolerability_context_with_ALT_AST_BUN_CK_and_organ_weight_monitoring,Potential Impact,ASO|RNase_H1_gapmer|cEt|phosphorothioate|subcutaneous|GYS1|Pompe|ERT_combination,WEISS_GYS1_ASO_POMPE_PREPRINT_2024,supporting_extrahepatic_ASO_gapmer_safety_and_ALT_AST_monitoring_context,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,2024,supporting,supporting_context_with_preprint_caution,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_hepatobiliary_injury_and_fibrosis_context_with_ALT_ALP_bilirubin_cholesterol_recovery_endpoints,Potential Impact,cholestasis|cholangiocyte|CX3CL1_CX3CR1|macrophage|NFY|TGFB1|ALT_ALP_bilirubin|fibrosis|siRNA_NFYA_context,OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,supporting_cholestatic_liver_injury_cholangiocyte_macrophage_fibrosis_context,Dynamic cholangiocyte responses in a murine model of reversible cholestasis: macrophage remodeling and NF-Y-mediated TGFβ1 expression,2025,direct,supporting_liver_pathobiology_context_not_direct_oligo_toxicity,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_preclinical_oligonucleotide_liver_toxicity_evidence_with_dose_sequence_dependence_and_reversibility,Potential Impact,AmNA_modified_ASO|phosphorothioate|PCDHA11|gastric_cancer|mouse_toxicology|ALT_AST_ALP|bilirubin|renal_markers|offtarget_screening,KANDA_PCDHA11_AMNA_ASO_2024,direct_preclinical_AmNA_modified_PCDHA11_ASO_sequence_dependent_reversible_hepatotoxicity_evidence,Dual-modified antisense oligonucleotides targeting oncogenic protocadherin to treat gastric cancer,2024,direct,yes_direct_hepatotoxicity_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_oligonucleotide_toxicity_mechanism_not_liver_specific,Potential Impact,phosphorothioate_ASO|LNA_gapmer|PS_body|DNA-PKcs|ATM|ATR|PARP1|DNA_damage_response,HJELMGREN_PS_ASO_DDR_2026,PS_ASO_DNA_damage_response_phase_separation_toxicity_mechanism,Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides,2026,direct,yes_direct_mechanistic_toxicity_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_targeted_siRNA_delivery_and_disease_context_with_liver_function_readouts,Potential Impact,siRNA|GalNAc|ASGPR|ROS-responsive_nanoparticle|PEI|MASH|Rubicon|lipophagy|ALT_AST,LAN_SIRUBICON_ROS_GALNAC_MASH_2025,ROS_responsive_GalNAc_hepatocyte_siRNA_delivery_MASH_lipophagy_safety_context,Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis,2025,supporting,yes_supporting_delivery_liver_function_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_ASO_chemistry_hepatotoxicity_reduction_evidence,Potential Impact,gapmer_ASO|LNA|BNA|scpBNA|scpBNA2|phosphorothioate_reduction|ALT_AST|nuclease_stability,YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,scpBNA_scpBNA2_gapmer_ASO_chemistry_reduced_PS_lower_hepatotoxicity,"Cycloalkane Incorporation Into the 2′,4′-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides",2025,direct,yes_direct_chemistry_safety_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_liver_injury_RNAi_intervention_and_readout_context,Potential Impact,siRNA|LNP|CYP2E1|APAP|DILI|ALT_AST|ROS|MDA|SOD|GSH|PPAR|IL6_IL1B_TNFA,LIU_CYP2E1_LNP_APAP_AILI_2025,siCyp2e1_LNP_APAP_acute_liver_injury_ALT_AST_oxidative_stress_inflammation_recovery,Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo,2025,direct,yes_direct_liver_injury_RNAi_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_delivery_cell_type_targeting_offtarget_liver_distribution_context,Potential Impact,DNA_origami_NANP|siRNA_delivery|cholesterol_lipidation|TriGalNAc|LDLR|SR-B1|ASGPR|HepG2|LSEC|Kupffer,KIM_NANP_LIPID_LIVER_TARGETING_2026,NANP_lipid_functionalization_GalNAc_LDLR_SR-B1_liver_cell_type_targeting_offtarget_uptake,Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting,2026,supporting,yes_supporting_delivery_targeting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_cell_RNAi_platform_safety_and_offtarget_context,Potential Impact,RNA_nanoparticle|RNAi|Hep3B|hTERT|BIRC5|FGFR1|apoptosis|migration|xenograft|offtarget_toxicity,SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,self_assembling_RNA_nanoparticle_Hep3B_hTERT_BIRC5_FGFR1_multitarget_RNAi_safety_context,Design of Anti-Tumor RNA Nanoparticles and Their Inhibitory Effect on Hep3B Liver Cancer,2026,supporting,yes_supporting_liver_RNAi_platform_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_modification_delivery_safety_and_offtarget_design_context_not_direct_liver_toxicity,Potential Impact,asiRNA|MYC|docosanoic_acid|cholesterol|vinylphosphonate|2prime_OMe|2prime_F|PS|RRM2|RAD51|PARP1|offtarget_reduction,MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,asymmetric_siRNA_VP_DCA_cholesterol_extrahepatic_delivery_durable_knockdown_safety_context,"Design, Screening and Development of Asymmetric siRNAs Targeting the MYC Oncogene in Triple-Negative Breast Cancer",2025,direct,yes_supporting_siRNA_design_safety_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_delivery_design_and_gene_silencing_context_not_liver_specific,Potential Impact,HDO|ASO_RNA_heteroduplex|folate|peptide|HeLa|GFP|BCL2|intracellular_delivery,SOUSA_HDO_MULTIFUNCTIONAL_HELA_2022,heteroduplex_ASO_multifunctionalization_folate_peptide_delivery_gene_silencing_context,Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells,2022,supporting,yes_supporting_delivery_design_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",supporting_chemistry_feasibility_context_already_covered_by_direct_scpBNA2_hepatotoxicity_module,Potential Impact,scpBNA2|BNA|LNA|purine_nucleosides|ASO_chemistry|nuclease_stability,KUMAGAI_SCPBNA2_PURINE_SYNTHESIS_2025,scpBNA2_full_monomer_synthesis_T_G_A_chemistry_context,"Development of Synthetic Routes to 2-O,4-C-Spirocyclopentylene-Bridged Nucleic Acids: Thymidine, Guanosine, and Adenosine",2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",potential_supporting_liver_injury_RNAi_context_but_deferred_due_to_extraction_quality,Potential Impact,shRNA|AAV|Bmp1|CCl4|liver_fibrosis|ALT_AST|collagen|alpha_SMA,BJD_BMP1_SHRNA_AAV_CCL4_FIBROSIS_CONTEXT,Bmp1_shRNA_AAV_CCl4_liver_fibrosis_ALT_AST_context_needs_manual_review,Protective effect of knockdown Bmp1 gene on carbon tetrachloride-induced liver fibrosis in mice,2025,deferred,triage_deferred_until_better_extraction,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,directly_relevant_liver_targeted_siRNA_toxicology_offtarget_safety_and_predictive_model_gap,Potential Impact,GalNAc-siRNA|AGT|2prime-F|2prime-MOE|VP|PS|offtarget_screening|RNAseq_toxicology|ALT_AST|kidney_safety|monkey_PKPD|Zilebesiran_comparator,HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,complete_GalNAc_siRNA_development_workflow_sequence_screening_modification_pattern_delivery_toxicology_offtarget_PKPD,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen",2025,direct,yes_direct_siRNA_design_toxicology_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_direct_liver_injury_immunomodulatory_oligodeoxynucleotide_module_for_APAP_context_and_macrophage_toxicology,Potential Impact,CpG_ODN|ODN1826|TLR9|NF-kB|IRG1|ACOD1|itaconate|APAP|macrophage|Kupffer_cell|Nrf2|ROS|apoptosis,QU_CPG_ODN_APAP_TLR9_IRG1_2025,CpG_ODN_TLR9_macrophage_immunomodulation_APAP_liver_injury_IRG1_itaconate_context,CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway,2025,direct,yes_supporting_ODN_immunomodulatory_liver_injury_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_oligonucleotide_ADME_biodistribution_and_tissue_PK_context_not_intrinsic_hepatotoxicity,Potential Impact,DNA_aptamer|ERBB2|PET|fluorine-18|complementary_oligonucleotide_platform|biodistribution|organ_PK|kidney_liver_excretion|tumor_visualization,PARK_ERBB2_APTAMER_PET_PK_2023,oligonucleotide_aptamer_PET_tissue_PK_biodistribution_target_specificity_excretion_context,In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging,2023,supporting,yes_supporting_oligo_PK_biodistribution_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",context_only_liver_cancer_target_biology_not_oligo_toxicity,Potential Impact,siRNA|DGAT1|HCC|single_cell_ATAC|single_cell_RNA|chromatin_accessibility|tumor_stroma,XI_HCC_CHROMATIN_DGAT1_SIRNA_2025,HCC_chromatin_accessibility_DGAT1_siRNA_functional_validation_context,Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",context_only_liver_inflammation_network_not_oligo_therapeutic_toxicity,Potential Impact,ceRNA|lncRNA|miRNA|mRNA|autoimmune_hepatitis|ConA|ALT_AST|MDA|NO|MAPK,LI_AIH_CERNA_NETWORK_2022,autoimmune_hepatitis_lncRNA_miRNA_mRNA_network_ALT_AST_MDA_NO_context,Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis,2022,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_high_value_ASO_hepatotoxicity_mitigation_and_offtarget_mechanism_module,Potential Impact,ASO|PNA|BROTHERS|BRO|LNA_gapmer|GalNAc|toehold_mediated_strand_displacement|protein_binding|hybridization_offtarget|ALT|Pcsk9,TERADA_BROTHERS_ASO_PNA_TOEHOLD_2023,BROTHERS_ASO_PNA_toehold_duplex_reduces_protein_binding_RNA_offtarget_and_ALT_hepatotoxicity,Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry,2023,direct,yes_direct_ASO_toxicity_mitigation_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_high_value_liver_targeted_siRNA_design_duration_and_tolerability_module,Potential Impact,GalNAc-siRNA|APOC3|2prime-F|2prime-OMe|2prime-MOE|PS|VP|AGO2_RISC|duration|rodent|nonhuman_primate|plozasiran_surrogate,PRAKASH_APOC3_LONG_ACTING_GALNAC_SIRNA_2025,APOC3_GalNAc_siRNA_chemical_scaffold_SAR_potency_duration_selectivity_tolerability_rodent_NHP,Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia,2025,direct,yes_direct_siRNA_SAR_safety_duration_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_high_value_bioanalysis_PK_TK_and_open_dataset_measurement_quality_module,Potential Impact,GalNAc-siRNA|LC-MS/MS|DPPT|plasma|givosiran|lumasiran|inclisiran|vutrisiran|metabolite|LLOQ|recovery|PK,KIM_GALNAC_SIRNA_LCMS_DPPT_2025,GalNAc_siRNA_quantification_DPPT_LCMS_PK_TK_bioanalysis_reproducibility_context,Differential Protein Precipitation-Based GalNAc-siRNA Sample Preparation with LC/MS Method Development Workflow in Plasma,2025,supporting,yes_supporting_bioanalysis_reproducibility_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_delivery_fibrosis_and_modified_nucleic_acid_safety_context,Potential Impact,modified_microRNA|miR-29a-3p|RNA-DNA_hybrid|2prime-F|LNA|PS|COL1A1|PDGFC|CCl4|liver_fibrosis|oral_delivery|no_DDS,UMEZU_ORAL_MIR29A_LIVER_FIBROSIS_NA_2025,oral_nuclease_resistant_miR29a_like_RNA_DNA_hybrid_LNA_PS_liver_fibrosis_COL1A1_PDGFC,Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis,2025,supporting,yes_supporting_liver_fibrosis_modified_NA_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",supporting_liver_cancer_RNAi_biosafety_context_but_redundant_with_existing_Hep3B_RNA_nanoparticle_modules,Potential Impact,multi-siRNA|branched_RNA|GP73|hTERT|Hep3B|Dicer|intratumoral|liver_toxicity_monitoring|IL4|IL6,LU_GT_MULTI_SIRNA_HCC_2025,dual_gene_branched_multi_siRNA_HCC_GP73_hTERT_biosafety_context,Development of a Dual Gene-Targeted Multi-Sirna with Branched Structure and Its Role in the Therapy of Liver Cancer,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_high_value_liver_targeted_nucleic_acid_delivery_and_long_term_safety_module,Potential Impact,LNP|Cas9_mRNA|sgRNA|CRISPR|HAO1|Hao1|PH1|glycolate_oxidase|urinary_oxalate|liver_delivery|off_target|immune_response|12_month_followup,JIANG_LNP_CRISPR_HAO1_PH1_2025,LNP_Cas9_mRNA_sgRNA_liver_delivery_HAO1_Hao1_PH1_urinary_oxalate_offtarget_liver_toxicity_immune_response_long_term,Efficient and safe in vivo treatment of primary hyperoxaluria type 1 via LNP-CRISPR-Cas9-mediated glycolate oxidase disruption,2025,supporting,yes_supporting_liver_delivery_safety_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_ASO_chemistry_internalization_and_cell_toxicity_context_not_liver_specific,Potential Impact,antisense_oligonucleotide|phosphothioate|LNA|HIV|MT4|cell_viability|internalization|FAM_uptake|vehicle_free_delivery|IC50,GOTFRID_PS_LNA_HIV_ASO_ACTIVITY_2026,PS_ASO_vs_PS_LNA_ASO_internalization_cytotoxicity_antiviral_activity_cellular_uptake_vehicle_free_context,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1,2026,supporting,yes_supporting_ASO_chemistry_tolerability_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",context_liver_lipid_metabolism_and_siRNA_validation_but_not_oligo_toxicity_or_human_oligo_safety,Potential Impact,siRNA|MAPK1|FGF21|bovine_hepatocytes|BHB|lipid_accumulation|ketosis|hepatic_lipid_metabolism,XU_FGF21_MAPK1_DAIRY_KETOSIS_SIRNA_2025,BHB_bovine_hepatocyte_MAPK1_siRNA_lipid_metabolism_FGF21_context,FGF21-MAPK1 Imbalance Disrupts Hepatic Lipid Metabolism in Dairy Cow Ketosis,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",review_context_not_primary_dataset_or_toxicology_module,Potential Impact,ASO|siRNA|miRNA|RNAi|RISC|RNase_H|splicing|delivery|GalNAc|LNP|cancer,ELGHAZZI_GENE_SILENCING_GI_GU_TUMORS_REVIEW_2025,ASO_siRNA_miRNA_mechanisms_delivery_modifications_clinical_oncology_review_context,"Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors",2025,deferred,triage_deferred_review_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",review_context_low_direct_fit_for_oligo_hepatotoxicity_dataset,Potential Impact,piRNA|PIWI|cancer|diagnostics|therapeutics|biomarker|LNA_antisense|nanoparticle_delivery,YANG_PIRNA_CANCER_DIAGNOSTIC_THERAPEUTIC_REVIEW_2026,piRNA_PIWI_cancer_diagnostics_therapeutics_review_context,Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics,2026,deferred,triage_deferred_review_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_high_value_siRNA_seed_mediated_offtarget_hepatotoxicity_and_safety_mitigation_module,Potential Impact,GalNAc-siRNA|ESC+|GNA|2-5-RNA|seed_region|RISC|off_target|ALT|hepatotoxicity|ALN-HBV|VIR-2218|rat_safety|healthy_volunteer_ALT,SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,GalNAc_siRNA_ESCplus_GNA_2_5_RNA_seed_pairing_destabilization_RNAi_offtarget_hepatotoxicity_ALT_ALN_HBV_VIR2218,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,2022,direct,yes_direct_high_value_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_chemistry_module_for_backbone_charge_PS_reduction_bioavailability_and_toxicity_design_space,Potential Impact,LNA|phosphothiotriester|PTTE|splice_switching_oligonucleotide|charge_neutral_backbone|click_conjugate|gymnosis|duplex_stability|amino_acid_conjugate,DHARA_LNA_PHOSPHOTHIOTRIESTER_SSO_CLICK_2025,LNA_phosphothiotriester_charge_neutral_backbone_click_conjugates_duplex_stability_gymnosis_splice_switching_bioactivity,Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages,2025,supporting,yes_supporting_chemistry_design_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_injury_pathway_module_not_oligo_specific_but_useful_for_liver_toxicity_mechanistic_covariates,Potential Impact,DILI|triptolide|ALT|AST|JNK|FXR|G0s2|siRNA|bile_acid|fatty_acid|carnitine|metabolic_disorder|oxidative_stress,LI_FXR_JNK_G0S2_TRIPTOLIDE_HEPATOTOXICITY_2025,triptolide_DILI_ALT_AST_JNK_FXR_G0s2_bile_acids_lipids_carnitine_siRNA_in_vitro_metabolic_hepatotoxicity_context,FXR as a pivotal role linking JNK and G0s2 mitigates triptolide-induced hepatotoxicity through the regulation of metabolic disorder of liver,2025,supporting,yes_supporting_liver_injury_pathway_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",context_HCC_lipid_metabolism_siRNA_but_not_therapeutic_oligo_toxicity_or_delivery_safety,Potential Impact,siRNA|COP1|HCC|lipid_metabolism|stemness|AKR1D1|TMEM65|ROS,JEON_COP1_HCC_LIPID_STEMNESS_SIRNA_2026,COP1_siRNA_HCC_lipid_metabolism_stemness_AKR1D1_TMEM65_context,Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,duplicate_of_direct_high_value_source,Potential Impact,duplicate_ESCplus_GalNAc_siRNA_seed_pairing_safety,SCHLEGEL_GKAC539_DUPLICATE_UPLOAD_2022,duplicate_upload_skipped,Duplicate upload of From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,2022,direct,triage_duplicate_not_added_as_separate_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_high_value_ASO_hepatotoxicity_mechanism_module,Potential Impact,ASO|gapmer|LNA|cEt|MOE|RNase_H1|off_target|very_long_pre_mRNA|ALT|AST|transaminitis|transcriptomics,BUREL_GAPMER_RNASEH1_LONG_PREMRNA_HEPATOTOX_2016,high_affinity_gapmer_LNA_cEt_RNaseH1_promiscuous_offtarget_very_long_pre_mRNA_ALT_AST_hepatotoxicity_mechanism,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts,2016,direct,yes_direct_high_value_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",measurement_quality_reproducibility_PK_biodistribution_module_for_ASO_payload_quantification,Potential Impact,ASO|antibody_oligonucleotide_conjugate|Fab_ASO|hybridization_LC-MS/MS|free_payload|PK|PD|biodistribution|tissue_matrix|linker_interference,JIANG_AOC_FREE_ASO_PAYLOAD_HYBRIDIZATION_LCMS_2024,free_ASO_payload_AOC_Fab_ASO_hybridization_LCMS_tissue_PK_biodistribution_parent_linker_interference_methodology,Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS,2024,supporting,yes_supporting_measurement_quality_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting_liver_fibrosis_lipotoxicity_and_RNA_tool_context_not_direct_therapeutic_oligo_toxicity,Potential Impact,siRNA|shRNA|AAV8|PUM1|exosome|MASLD|HSC_activation|fibrosis|TPM4|lipotoxicity|hepatocyte_stress,WAN_PUM1_EXOSOMES_MASLD_HSC_FIBROSIS_2025,PUM1_hepatocyte_exosome_MASLD_lipotoxic_death_HSC_activation_TPM4_translation_AAV8_shRNA_siRNA_context,Hepatocyte-derived Pumilio1-enriched exosomes inhibit HSC activation by suppressing tropomyosin-4 translation,2025,direct,yes_supporting_liver_fibrosis_context_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",context_HCC_target_validation_but_not_therapeutic_oligo_toxicity_or_delivery_safety,Potential Impact,siRNA|HMMR|HCC|4-MU|drug_resistance|xenograft|migration|proliferation,ZHU_HMMR_HCC_4MU_SIRNA_2026,HMMR_siRNA_HCC_drug_resistant_cell_proliferation_migration_4MU_context,HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",low_direct_value_for_OligoTox_liver_toxicity_prediction,Potential Impact,aptamer|SELEX|drug_delivery|diagnostics|breast_cancer|nanoparticle_conjugate,GHOLIKHANI_APTAMER_BREAST_CANCER_REVIEW_2022,aptamer_delivery_diagnostics_therapeutics_review_context,"Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics",2022,deferred,triage_deferred_review_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_clinical_ASO_ALT_and_hepatocyte_killing_context,Potential Impact,unconjugated_ASO|HBV|ALT|HBsAg|immune_biomarkers|transcriptomics|proteomics,JOSHI_BEPIROVIRSEN_B_TOGETHER_IMMUNOMODULATION_2026,direct_ASO_clinical_ALT_immunomodulation_module,Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study),2026,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_systemic_ASO_safety_and_liver_damage_comparator_context,Potential Impact,SNA-ASO|gapmer|PS|MOE comparator|SGLT2|kidney uptake|liver safety,TSUBOI_SNA_ASO_SGLT2_KIDNEY_SYSTEMIC_SAFETY_2025,supporting_ASO_chemistry_delivery_safety_module,In vivo efficacy and safety of systemically administered serinol nucleic acid-modified antisense oligonucleotides in mouse kidney,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_RNA_delivery_safety_and_liver_transfection_context,Potential Impact,LNP|polyamine|mRNA|siRNA|endosomal_escape|factor_VII|liver_delivery|toxicity,KANNAN_POLYAMINE_PLNP_RNA_DELIVERY_SAFETY_2025,supporting_LNP_RNA_delivery_safety_module,Incorporation of a polyamine into lipid nanoparticles increases the endosomal release and transfection of nucleic acids without toxicity,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_not_oligo_specific_liver_metabolism_context,Potential Impact,peptide|GALP|HFD|liver transcriptome|metabolome|bile acids|fatty acid metabolism,TAKENOYA_GALP_HFD_LIVER_TRANSCRIPTOME_METABOLOME_2023,deferred_liver_metabolism_context,Transcriptomic and metabolome analyses of liver in high-fat diet mice after intranasal GALP,2023,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_review_only_background,Potential Impact,siRNA|LNP|GalNAc|approved therapeutics|clinical trials,SHEVELEV_SIRNA_THERAPEUTICS_REVIEW_2025,deferred_review_context,siRNA therapeutics for the treatment of hereditary diseases and other conditions: A review,2025,deferred,triage_deferred_review_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_ASO_liver_toxicity_and_off_target_safety_assessment,Potential Impact,RNase_H1_ASO|LNA_gapmer|off-target|RNAseq|proteomics|ALT|HepG2|time_course,VAN_LEEUWEN_ASO_MULTIOMICS_TIME_RESOLVED_SAFETY_2026,direct_ASO_safety_transcriptomics_proteomics_module,Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach,2026,direct,yes_direct_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_preclinical_GalNAc_siRNA_liver_kidney_safety_and_toxicology_context,Potential Impact,GalNAc-siRNA|LPA|Lp(a)|rat|NHP|PK|TK|off-target|ALT|ALP|cytokine|complement,RIDER_SLN360_LPA_GALNAC_SIRNA_PRECLINICAL_TOX_2022,direct_GalNAc_siRNA_preclinical_safety_module,"Preclinical Toxicological Assessment of A Novel siRNA, SLN360, Targeting Elevated Lipoprotein(a) in Cardiovascular Disease",2022,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_injury_inflammation_and_targeted_siRNA_delivery_context,Potential Impact,siRNA|BRCC3|Kupffer_cell|ZIF-8|extracellular_vesicle|NLRP1|sepsis_liver_injury|LPS|CLP,MA_KUPFFER_BIOMIMETIC_ZIF8_BRCC3_SIRNA_SRLI_2025,supporting_siRNA_liver_injury_nanoparticle_delivery_module,Kupffer cells biomimetic nanoparticles alleviate sepsis related liver injury,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_low_direct_oligotox_hepatotoxicity_signal,Potential Impact,ASO|splice_switching|PKHD1|ARPKD|pseudoexon|kidney|hepatic_fibrosis,LI_PKHD1_ARPKD_ASO_SPLICE_RESCUE_2023,deferred_ASO_splicing_rare_disease_context,A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease,2023,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_diagnostic_liver_disease_context_not_therapeutic_oligo_toxicity,Potential Impact,oligonucleotide_microarray|ATP7B|Wilson_disease|diagnostics|mutation_detection,JIA_ATP7B_WILSON_MICROARRAY_DIAGNOSTIC_2022,deferred_liver_genetic_diagnostics_context,Laboratory and clinical evaluation of a microarray for the detection of ATP7B mutations in Wilson disease in China,2022,deferred,triage_deferred_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_ASO_therapeutic_context_and_splice_switching_design_features,Potential Impact,MOE_PS_ASO|splice_switching|exon_skipping|EZH2|HCC|xenograft|liver_accumulation|H3K27me3,BAI_EZH2_EXON_SKIPPING_HCC_ASO_2025,supporting_liver_ASO_splice_switching_efficacy_module,Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_extrahepatic_delivery_and_biodistribution_context_for_oligo_safety_modeling,Potential Impact,DNA_RNA_HDO|gapmer_ASO|alpha_tocopherol|DRG|sciatic_nerve|systemic_delivery|RNase_H1,KABURAGI_TOC_HDO_DRG_SCIATIC_SYSTEMIC_DELIVERY_2022,supporting_extrahepatic_ASO_HDO_delivery_module,Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve,2022,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_fibrosis_HSC_activation_ferroptosis_and_RNA_perturbation_context,Potential Impact,lncRNA|siRNA|shRNA|XIST|miR-663a|GPX4|HSC|ferroptosis|ALT|AST|HYP|hepatic_fibrosis,DAI_XIST_MIR663A_GPX4_HSC_FERROPTOSIS_FIBROSIS_2026,supporting_RNA_perturbation_HSC_ferroptosis_fibrosis_module,Long noncoding RNA X-inactive-specific transcript promotes hepatic fibrosis by suppressing ferroptosis in hepatic stellate cells via the miR-663a/GPX4 axis,2026,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_useful_liver_targeting_and_fibrosis_context_but_not_oligonucleotide_therapeutic,Potential Impact,GalNAc|ASGPR|PROTAC|BRD4|HSC|fibrosis|CCl4|CDAA-HFD|transcriptomics|metabolomics,YUAN_LIVTAC_GALNAC_PROTAC_BRD4_FIBROSIS_2025,deferred_GalNAc_non_oligo_liver_targeting_context,Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_liver_injury_pathway_context_but_non_oligo_nutraceutical_intervention,Potential Impact,ethanol_liver_injury|PPAR-alpha|NLRP3|caspase-1|pyroptosis|siRNA_control,CAI_LYCIUM_POLYSACCHARIDES_ETHANOL_LIVER_INJURY_2025,deferred_non_oligo_hepatoprotection_context,Lycium barbarum Polysaccharides Alleviate Ethanol-Induced Liver Injury by Activating PPAR-alpha and Inhibiting NLRP-3/Caspase-1-Mediated Pyroptosis,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_liver_targeted_siRNA_safety_offtarget_and_MASH_fibrosis_readout_context,Potential Impact,GalNAc-siRNA|CIDEB|MASH|MASLD|ASGPR|2prime-OMe|2prime-F|5prime-VP|isoGNA|off-target|steatosis|fibrosis|liver_toxicity,LIN_GALNAC_SICIDEB_MASH_STEATOSIS_FIBROSIS_2025,direct_liver_GalNAc_siRNA_MASH_safety_efficacy_module,Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models,2025,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_cross-organ_ASO_toxicity_mechanism_and_chemistry_mitigation_context,Potential Impact,gapmer_ASO|PS|LNA|MOE|2prime-OMe|5prime-cyclopropylene|late-onset_neurotoxicity|p53|paraspeckle|p54nrb|chemical_mitigation,KURODA_ASO_LATE_ONSET_NEUROTOX_5CP_MODIFICATIONS_2025,direct_ASO_toxicity_mitigation_chemistry_module,Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications,2025,supporting,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_liver_GalNAc_siRNA_safety_and_functional_liver_homeostasis_context,Potential Impact,GalNAc-siRNA|C/EBPbeta|MASLD|steatosis|liver_function|albumin|bilirubin|ALT|AST|hepatocyte_delivery,KHORSANDI_GALNAC_SICEBPB_MASLD_HOMEOSTASIS_2026,direct_liver_GalNAc_siRNA_MASLD_safety_homeostasis_module,GalNAc-conjugated siRNA targeting C/EBPbeta reverses metabolic dysfunction and restores liver homeostasis in a murine MASLD model,2026,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_delivery_chemistry_and_liver_distribution_context_for_large_oligonucleotides,Potential Impact,SS-ODN|trivalent_disulfide_unit|thiol_exchange|cellular_uptake|liver_distribution|endocytosis_independent|low_cytotoxicity,WANG_TRIVALENT_DISULFIDE_MASKED_ODN_DELIVERY_2024,supporting_oligonucleotide_delivery_chemistry_module,Trivalent Disulfide Unit-Masked System Efficiently Delivers Large Oligonucleotide,2024,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_not_oligonucleotide_not_liver_toxicity_specific,Potential Impact,NSCLC|microarray|WES|survival|SWI/SNF|VISTA|chemotherapy_response,NASTASE_NSCLC_LONG_TERM_SURVIVAL_MARKERS_2022,deferred_non_oligo_NSCLC_genomics_context,Molecular Markers for Long-term Survival in Stage IIIA (N2) NSCLC Patients,2022,deferred,triage_deferred_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_liver_injury_mechanism,Potential Impact,siRNA|AAV|MASH|macrophage_pyroptosis|NLRP3,ZHANG_MPTP_OXMTDNA_MASH_ITPR3_NLRP3_2025,supporting_liver_injury_pyroptosis_mechanism,MPTP mediated Ox-mtDNA release inducing macrophage pyroptosis and exacerbating MCD-induced MASH via ITPR3/Ca2+/NLRP3 pathway,2025,supporting,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct_liver_injury_fibrosis_readouts,Potential Impact,siRNA|Cspg4|NG2|liver_fibrosis|ALT_AST,YANG_NG2_CSPG4_SIRNA_LIVER_FIBROSIS_2023,direct_siRNA_liver_fibrosis_module,Neuron-Glial Antigen 2 participates in liver fibrosis via regulating BMSC differentiation to myofibroblast,2023,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting_delivery_biodistribution_and_liver_offtarget_context,Potential Impact,LNP|mRNA_delivery|tumor_tropism|liver_offtarget_delivery,HUAYAMARES_HNSCC_LNP_TUMOR_TROPISM_LIVER_DETARGET_2023,supporting_LNP_biodistribution_liver_detargeting_module,High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo,2023,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_review_only,Potential Impact,siRNA|nanoparticles|oncology_delivery,HUANG_NANOPARTICLE_SIRNA_ONCOLOGY_REVIEW_2022,deferred_review_context,Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic siRNA in Precision Oncology,2022,deferred,triage_deferred_review_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred_review_only,Potential Impact,ASO|chemistry|delivery|clinical_development,RUCHI_EVOLUTION_ASO_CHEMISTRY_DELIVERY_REVIEW_2025,deferred_review_context,Evolution of Antisense Oligonucleotides: Navigating Nucleic Acid Chemistry and Delivery Challenges,2025,deferred,triage_deferred_review_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting cross-organ ASO/siRNA pharmacology; not direct hepatotoxicity,Potential Impact,ASO|siRNA|NNMT|NAD|macrophage_proliferation|macrophage_apoptosis,SINHA_NNMT_ASO_MACROPHAGE_ATHEROSCLEROSIS_2025,supporting_systemic_ASO_macrophage_immunometabolism_module,NAD metabolism regulates proliferation of macrophages in atherosclerosis,2025,direct,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting RNA delivery/tolerability context; not direct hepatotoxicity,Potential Impact,synthetic_ncRNA|LNP|casein_chitosan_C2_micelles|oral_delivery|macrophages|monocytes|tolerability|liver_enzymes,YAMAGUCHI_TY1_ORAL_NCRNA_MACROPHAGE_C2_2025,supporting_oral_macrophage_active_ncRNA_delivery_safety_module,"Oral Bioavailability of a Noncoding RNA Drug, TY1, That Acts on Macrophages",2025,direct,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting delivery and biodistribution context beyond liver,Potential Impact,siRNA|RGD|dsRBD|18His|integrin_avb3|endosomal_escape|tumor_delivery|low_toxicity,YU_DUAL_RGD_DSRBD_18HIS_TUMOR_SIRNA_DELIVERY_2021,supporting_extrahepatic_tumor_targeted_siRNA_delivery_safety_module,Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery,2021,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",deferred: not therapeutic oligo liver-toxicity source,Potential Impact,lentiviral_shRNA|p21|cartilage|hepatic_offtarget_transduction,LARIJANI_P21_SHRNA_CARTILAGE_REPAIR_2026,deferred_lentiviral_shRNA_cartilage_context,p21 Knockdown as a Therapeutic Strategy for Focal Cartilage Injury Repair,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty","deferred: small-molecule antiviral, not oligo toxicity",Potential Impact,panduratin_A|HBV|HNF1alpha|siRNA_mechanistic_knockdown|3D_liver_spheroid,THONGSRI_PANDURATIN_A_HBV_HNF1A_2026,deferred_non_oligo_HBV_small_molecule_liver_context,Panduratin A suppresses hepatitis B virus by targeting HNF1alpha,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",liver/hepatocyte model context but not therapeutic oligo toxicity,Potential Impact,apilimod|PIKfyve|HEV_entry|siRNA_knockdown_mechanistic_validation,RING_PIKFYVE_APILIMOD_HEV_ENTRY_2026,deferred_non_oligo_host_directed_hepatocyte_antiviral_context,Phosphoinositide kinase PIKfyve inhibitor apilimod blocks hepatitis E virus infection,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",review-only and cardiac-focused; not direct OligoTox hepatotoxicity source,Potential Impact,RNAi|patisiran|revusiran|cardiac_failure|adverse_effects,SADDIQUE_RNAI_CARDIAC_FAILURE_SYSTEMATIC_REVIEW_2024,deferred_review_only_cardiac_RNAi_context,Safety and effectiveness of interference RNA based therapeutics in cardiac failure: A systematic review,2024,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting ASO/GapmeR modality and tolerability context outside liver; not direct hepatotoxicity,Potential Impact,LNA_GapmeR|pseudogene|RPSAP52|HMGA2|ovarian_cancer|PDOX|toxicity_context,RAMESH_KUMAR_RPSAP52_LNA_GAPMER_OVARIAN_PDOX_2025,supporting_gapmer_ASO_extrahepatic_oncology_safety_module,Specific targeting of the pseudogene RPSAP52 reduces ovarian tumor growth in patient-derived orthoxenograft models,2025,direct,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","supporting delivery, liver-targeting, RNA loading and safety/biocompatibility context",Potential Impact,EMNV|hybrid_EMNV_liposome|siRNA|PTGFRN|CD63|liver_targeting|RNA_loading|endosomal_escape,KOSTYUSHEVA_BIOLOGICS_HYB_TARGETED_RNA_DELIVERY_2025,supporting_EMNV_liposome_hybrid_siRNA_delivery_module,Biologics-based technologies for highly efficient and targeted RNA delivery,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",useful clinical ASO background but review-only; not row-level source,Potential Impact,pelacarsen|GalNAc_ASO|LPA|apo(a)|Lp(a)|ASCVD|clinical_safety,BHATIA_PELACARSEN_LPA_ASO_REVIEW_2025,deferred_review_only_pelacarsen_clinical_ASO_context,Pelacarsen: Mechanism of action and Lp(a)-lowering effect,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",primary hepatocyte delivery context but not therapeutic oligo toxicity data,Potential Impact,Gag.MS2|Cas9_mRNA|sgRNA|primary_hepatocytes,BARON_ALPHA_GAG_MS2_CRISPR_RNA_DELIVERY_2022,deferred_gene_editing_vector_delivery_context_only,Improved alpharetrovirus-based Gag.MS2 particles for efficient and transient delivery of CRISPR-Cas9 into target cells,2022,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",general diagnostics rigor context but not oligo therapeutic toxicity data,Potential Impact,microarray|gene_expression|machine_learning|transplant_rejection,MADILL_HALLORAN_MMDX_TRANSPLANT_DIAGNOSTICS_2024,deferred_diagnostics_and_machine_learning_context_only,Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope Diagnostic System,2024,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,"direct liver-targeted siRNA module with hepatocyte receptor silencing, durability, dose response, and infection-protection endpoints",Potential Impact,GalNAc-siRNA|CD81|hepatocyte|ASGPR|malaria_prevention|humanized_liver_mouse,STEEL_CD81_GALNAC_SIRNA_MALARIA_PROTECTION_2025,direct_liver_targeted_GalNAc_siRNA_hepatocyte_knockdown_module,Protection from malaria infection using liver-targeted siRNA,2025,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting dsRNA/TLR3/RIG-I/MDA5/interferon-response context for oligo immune-activation modeling,Potential Impact,RBM39|siRNA_knockdown|TLR3|RIG-I|MDA5|IRF3|STAT1|STAT2|IFN|poly(I:C),LI_RBM39_HEPATOCYTE_IFN_INNATE_IMMUNITY_2025,supporting_hepatocyte_interferon_and_oligo_immune_activation_module,RBM39 shapes innate immunity by controlling the expression of key factors of the interferon response,2025,supporting,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,"design, synthesis, hepatocyte delivery, specificity, comparator, and PCSK9 validation context for GalNAc-siRNA model-readiness",Potential Impact,GalNAc-siRNA|PCSK9|ASGPR|liquid-phase_conjugation|siRNA_design|Inclisiran_comparator,DMITRIEV_GALNAC_SIRNA_PCSK9_LIQUID_PHASE_2026,direct_GalNAc_siRNA_design_synthesis_and_PCSK9_validation_module,Refined Design and Liquid-Phase Assembly of GalNAc-siRNA Conjugates: Comparative Efficiency Validation in PCSK9 Targeting,2026,direct,yes_direct_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct liver-fibrosis RNAi intervention and collagen/fibrogenic readout context in human MASH/MetALD models,Potential Impact,Dicer substrate siRNA|LARP6|HSC|MASH|MetALD|collagen|3D liver spheroids,KIM_LARP6_HSC_FIBROSIS_DSI_RNA_2026,direct_HSC_fibrosis_dsiRNA_and_human_MASH_MetALD_spheroid_module,RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis,2026,direct,yes_direct_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supports dose-control and reversibility concepts for liver-directed RNAi and gene-therapy safety engineering,Potential Impact,GalNAc-siRNA|shRNA|REVERSIR|AAV8|hepatocyte transgene expression|dose control,SUBRAMANIAN_RNAI_RHEOSTAT_AAV_TRANSGENE_2023,supporting_GalNAc_siRNA_REVERSIR_AAV_expression_control_module,RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes,2023,direct,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",background only; not used for row-level data generation,Potential Impact,siRNA design|chemical modification|delivery|clinical landscape,FRIEDRICH_AIGNER_THERAPEUTIC_SIRNA_REVIEW_2022,deferred_background_review_only,Therapeutic siRNA: State-of-the-Art and Future Perspectives,2022,deferred,triage_deferred_context_only,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct mechanistic evidence that seed-driven RNAi off-target effects can drive GalNAc-siRNA rat hepatotoxicity and can be mitigated by destabilizing seed pairing,Potential Impact,GalNAc-siRNA|seed off-target|RISC loading|GNA modification|ALT|AST|rat hepatotoxicity,JANAS_GALNAC_SIRNA_OFFTARGET_RAT_HEPATOTOX_2018,direct_seed_offtarget_rat_hepatotoxicity_module,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity,2018,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","supports liver-toxicity modeling rigor, transcriptomic mechanism coverage, dose-resolved DILI prediction, and validation strategy",Potential Impact,primary human hepatocytes|RNA-seq|DILImap|ToxPredictor|DILI|machine learning|safety margins,BERGEN_DILIMAP_TOXPREDICTOR_DILI_2025,supporting_human_hepatocyte_DILI_modeling_and_validation_module,A large-scale human toxicogenomics resource for drug-induced liver injury prediction,2025,supporting,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,"direct clinical liver-targeted ASO safety, transaminase elevation, ASGPR saturation, narrow therapeutic-window context",Potential Impact,GalNAc-conjugated LNA ASO|PAPD5|PAPD7|HBV|HBsAg|transaminases|PK/PD,GERETTI_RO7239958_GALNAC_LNA_ASO_HBV_PHASE1_2025,direct_clinical_LNA_ASO_PK_PD_safety_window_module,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",2025,direct,yes_direct_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,supporting delivery/tolerability context outside liver; useful for modality breadth and macrophage immune-delivery modeling rather than direct liver toxicity,Potential Impact,nebulized siRNA|hybrid lipid nanoparticles|TGFb1 siRNA|pulmonary fibrosis|macrophage delivery|mucus barrier,LIU_HYDROGEN_HNP_TGFB1_SIRNA_PULMONARY_FIBROSIS_2025,supporting_extrahepatic_nebulized_siRNA_delivery_and_macrophage_safety_module,Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis,2025,direct,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supports hepatic immune-toxicity mitigation logic and tissue-selective innate immune activation using siRNA co-therapy,Potential Impact,PCSK9 siRNA|STING agonist|innate immunity|liver toxicity mitigation|nanoparticle co-delivery,SUN_PCSK9_SIRNA_STING_CANCER_IMMUNOTHERAPY_2025,supporting_siRNA_STING_hepatic_immune_toxicity_modulation_module,Silencing PCSK9 reshapes the spatiotemporal activation of STING for safe and effective cancer immunotherapy,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty","HCC target-validation biology; lower value for oligo-toxicity modeling than clinical ASO, delivery, or toxicity-mechanism sources",Potential Impact,siRNA knockdown|TOP2A|HCC|scRNA-seq|HepG2|Huh7,XIE_TOP2A_HCC_SCRNA_SIRNA_KNOCKDOWN_2025,deferred_HCC_target_validation_context_only,Single cell-RNA sequencing reveal TOP2A as a key driver of hepatocellular carcinoma progression,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting extrahepatic ASO specificity and tissue-effect context; useful for safety-boundary modeling and distinguishing liver vs muscle ASO effects,Potential Impact,gapmer ASO|GYS1|Pompe disease|skeletal muscle|ERT combination|substrate reduction,WEISS_GYS1_ASO_POMPE_SKELETAL_MUSCLE_2025,supporting_extrahepatic_ASO_tissue_safety_and_substrate_reduction_module,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,2025,supporting,yes_supporting_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,"direct liver-targeted siRNA disease and safety context; links hepatocyte target knockdown to hepatic lipid injury, inflammation, steatosis, and MASH progression",Potential Impact,LNP-siRNA|SPTLC2|hepatocytes|MASH|ceramide|lipidomics|ALT_AST|fibrosis,YU_SPTLC2_LNP_SIRNA_MASH_CERAMIDE_2025,direct_hepatocyte_LNP_siRNA_MASH_ceramide_module,Targeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH,2025,direct,yes_direct_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting oligo delivery/selectivity and HCC immune microenvironment context; useful for modeling immune-targeted RNA therapeutics and off-tumor safety boundaries,Potential Impact,aptamer-siRNA chimera|PD-L1 aptamer|CD47 siRNA|Treg|HCC|tumor microenvironment|immune checkpoint,ZENG_PDL1_APTAMER_CD47_SIRNA_TREG_HCC_2025,supporting_cell_selective_aptamer_siRNA_immune_oncology_module,Targeting tumor-infiltrating regulatory T cells: combining CD47 and PD-L1 inhibition via a novel aptamer-siRNA chimera,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",supporting liver-injury/fibrosis biomarker and pathway context; siRNA used mechanistically to validate THBS1 effects on collagen/JAK2-STAT3 signaling,Potential Impact,siRNA knockdown|THBS1|RILI|TMT proteomics|JAK2_STAT3|COL5A|COL6A|plasma biomarker,WANG_THBS1_RILI_PROTEOMICS_SIRNA_2025,supporting_liver_injury_biomarker_and_fibrosis_mechanism_module,THBS1 as a candidate biomarker and fibrotic mediator in radiation-induced liver injury,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",liver injury biology but bovine ketosis and mechanistic siRNA use only; low direct value for therapeutic oligo toxicity modeling,Potential Impact,siRNA knockdown|NEDD4|RIPK1|NEFA|ketotic cows|bovine hepatocytes|NF-kB,LIU_NEDD4_NEFA_KETOTIC_COW_LIVER_2026,deferred_non_therapeutic_siRNA_bovine_ketosis_context,The E3 ubiquitin ligase NEDD4 protects against nonesterified fatty acid-induced hepatic inflammatory injury in ketotic cows,2026,deferred,triage_deferred_context_only,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",liver metabolic injury biology but bovine ketosis and mechanistic siRNA use only; low direct oligo-toxicity value,Potential Impact,siRNA knockdown|HNF4A|NEFA|FAO|CES1|CES2|ketotic cows|bovine hepatocytes,CHEN_HNF4A_KETOTIC_COW_HEPATOCYTE_SIRNA_2025,deferred_non_therapeutic_siRNA_bovine_ketosis_lipid_metabolism_context,The hepatic expression status of hepatocyte nuclear factor 4alpha in subclinical and clinical ketotic dairy cows and its impact on lipid metabolism in hepatocytes,2025,deferred,triage_deferred_context_only,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","adds bile-acid-induced hepatocyte apoptosis, transglutaminase/cytokeratin aggregation, caspase activation, and siRNA-based rescue context",Potential Impact,siRNA knockdown|TG1|TG2|K18|K8|GCDCA|hepatocyte apoptosis|cholestasis|fibrosis,TATSUKAWA_TG_KERATIN_BILE_ACID_HEPATOCYTE_DEATH_2025,supporting_bile_acid_hepatocyte_death_and_fibrosis_module,Transglutaminase-mediated cytokeratin modifications implicated in bile-acid-induced hepatocyte death,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","adds acute inflammatory/oxidative-stress liver injury, ALT/AST dysfunction, siRNA worsening, and rescue-pathway context",Potential Impact,siRNA knockdown|AAV9 overexpression|TRIM16|YAP1|Nrf2|ALT|AST|TNF-alpha|IL-6|oxidative stress,ZHANG_TRIM16_YAP1_NRF2_SEPTIC_LIVER_INJURY_2026,supporting_inflammation_oxidative_stress_liver_injury_module,TRIM16 mediates YAP1 K63-linked ubiquitination to alleviate sepsis-induced acute liver injury through YAP/Nrf2 axis in mice,2026,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","adds advanced hepatocellular-carcinoma siRNA delivery, targeting, trafficking, and transfection-efficiency context",Potential Impact,siRNA delivery|tumor-derived EV membrane|hybrid lipid nanovesicle|HCC|endosomal bypass|Golgi|ER|tumor homing,ZHOU_TDEV_MEMBRANE_LEV_SIRNA_HCC_DELIVERY_2022,supporting_EV_membrane_hybrid_siRNA_delivery_module,Tumour-derived extracellular vesicle membrane hybrid lipid nanovesicles enhance siRNA delivery by tumour-homing and intracellular freeway transportation,2022,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",general hepatic pharmacometabolism and hepatocyte-function context; lower direct relevance because therapeutic oligos are not mainly CYP-metabolized,Potential Impact,siRNA knockdown|primary human hepatocytes|NFI transcription factors|CYP activity|drug metabolism,KLEIN_NFI_CYP_HUMAN_LIVER_PHARMACOMETABOLISM_2025,deferred_general_CYP_drug_metabolism_context,Transcription factors of the Nuclear Factor I family control hepatocyte differentiation and cytochrome P450 activity in human liver,2025,deferred,deferred,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","adds copper-dependent hepatocyte injury, regulated cell death, LDH/ALT/AST injury context, and siRNA rescue of cuproptosis mediators",Potential Impact,siRNA knockdown|ATP7B knockout|cuproptosis|copper overload|ALT|AST|LDH|HepG2|Wilson disease,TANG_CUPROPTOSIS_WILSON_DISEASE_2025,supporting_cuproptosis_copper_induced_liver_injury_module,Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","adds mechanistic GalNAc-siRNA disposition, cross-species scaling, liver specificity, off-target organ accumulation, and clinical PK-PD translation context",Potential Impact,GalNAc-siRNA|PBPK|PK-PD|ASGPR|RISC|mouse|monkey|human|off-target organs|liver exposure,SALIM_GALNAC_SIRNA_WB_PBPK_PD_2025,direct_GalNAc_siRNA_PK_PD_species_translation_and_off_target_distribution_module,Whole-Body Physiologically Based Pharmacokinetic–Pharmacodynamic Modeling for Interspecies Translation and Mechanistic Characterization of Plasma and Tissue Disposition of GalNAc-siRNAs,2025,supporting,yes_supporting_module,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty","useful background on oligonucleotide pharmacology and HBV therapeutic classes, but review-only",Potential Impact,ASO|siRNA|NAP|HBV|immunostimulation|GalNAc|LNP|liver uptake|off-target effects,VAILLANT_HBV_OLIGONUCLEOTIDE_THERAPIES_REVIEW_2022,deferred_review_background_for_HBV_oligonucleotide_mechanisms,"Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects",2022,deferred,deferred,source_metadata_curated_generated
"tracked but not used as a full generation module because of limited fit, duplication, or extraction uncertainty",general high-order gene-expression methods; not therapeutic oligo toxicity or delivery evidence,Potential Impact,microarray|HCC|partial information decomposition|synergy clusters|mutual information|gene expression,LACALAMITA_PID_MICROARRAY_HIGH_ORDER_PATTERNS_2025,deferred_optional_notebook_method_context,Unveiling complex patterns: An information-theoretic approach to high-order behaviors in microarray data,2025,deferred,deferred,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,direct mechanistic source for RISC-mediated hybridization-based off-target activity and GalNAc-siRNA hepatotoxicity; distinguishes AGO2 on-target requirement from AGO2/TNRC6 off-target toxicity roles,Potential Impact,GalNAc-siRNA|AGO2|AGO1|AGO4|TNRC6A|TNRC6B|TNRC6C|RISC|seed_offtarget|hepatotoxicity,AGARWAL_GALNAC_SIRNA_OFFTARGET_2025,core_GalNAc_siRNA_RISC_AGO2_TNRC6_seed_offtarget_hepatotoxicity_module,Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates,2025,direct,yes_core_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","core chemistry and delivery reference for approved oligonucleotide therapeutics, chemical modifications, LNPs, and GalNAc hepatocyte targeting",Potential Impact,ASO|SSO|siRNA|aptamer|phosphorothioate|2prime_F|2prime_OMe|2prime_MOE|PMO|LNP|GalNAc,EGLI_MANOHARAN_APPROVED_OLIGO_CHEMISTRY_2023,core_reference_approved_oligonucleotide_chemistry_delivery_landscape_module,"Chemistry, Structure and Function of Approved Oligonucleotide Therapeutics",2023,supporting,yes_core_reference_module,source_metadata_curated_generated
direct oligo toxicity or liver-safety readouts useful for predictive modeling,"direct precision hepatology source for liver-targeted ASO target engagement, MASH biomarkers, hepatic fat response, and safety/tolerability context",Potential Impact,GalNAc-ASO|PNPLA3|MASH|148M_homozygous|liver_fat|hCRP|IL6|target_engagement|PK|PD,ARMISEN_AZD2693_PNPLA3_ASO_MASH_2025,core_PNPLA3_GalNAc_ASO_precision_MASH_target_engagement_module,"AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: Two randomized phase I trials",2025,direct,yes_core_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","supporting platform source for ASO/siRNA structural, chemical, pharmacokinetic, and mechanism distinctions relevant to safety modeling",Potential Impact,ASO|siRNA|Watson-Crick_hybridization|Ago2|RNase_H1|chemistry|delivery|structure_matters,CROOKE_RNA_TARGETED_THERAPEUTICS_2018,supporting_RNA_targeted_therapeutics_platform_mechanism_module,RNA-Targeted Therapeutics,2018,supporting,yes_supporting_platform_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","supports model-system selection, species/sequence alignment, surrogate versus humanized models, and interpretation of preclinical readouts",Potential Impact,ASO|siRNA|preclinical_models|surrogate_NAT|humanized_locus|patient_cells|in_vitro|in_vivo,OLIVER_HILL_MODEL_SELECTION_NAT_2026,supporting_preclinical_model_selection_NAT_methods_module,Model Selection in Preclinical Nucleic Acid Therapeutics Research,2026,supporting,yes_supporting_methods_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",current regulatory/approval landscape context; highlights continued clinical maturity of GalNAc hepatocyte-targeted oligonucleotide delivery,Potential Impact,approved_oligonucleotides|fitusiran|donidalorsen|plozasiran|GalNAc|subcutaneous|FDA_2025,ALSHAER_FDA_TIDES_HARVEST_2025,supporting_current_approved_oligonucleotide_landscape_module,2025 FDA TIDES (Peptides and Oligonucleotides) Harvest,2026,supporting,yes_supporting_landscape_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism",foundational human-genetics target rationale for HSD17B13 silencing strategies and liver-protection phenotypes,Potential Impact,HSD17B13|loss_of_function|ALT|AST|chronic_liver_disease|NASH|cirrhosis|PNPLA3_interaction|human_genetics,ABULHUSN_HSD17B13_PROTECTIVE_VARIANT_2018,core_HSD17B13_protective_human_genetics_target_rationale_module,A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease,2018,supporting,yes_core_module,source_metadata_curated_generated
"supporting delivery, mechanism, disease, or assay context that improves model realism","preclinical ASO source showing Hsd17b13 knockdown, steatosis modulation, and fibrosis-response limitations in a diet-induced NASH-like fibrosis model",Potential Impact,Hsd17b13_ASO|LNA_gapmer|phosphorothioate|CDAHFD|NASH|steatosis|fibrosis|primary_hepatocytes,MA_HSD17B13_ASO_FIBROSIS_MOUSE_2024,core_HSD17B13_ASO_preclinical_steatosis_fibrosis_limitations_module,Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model,2024,supporting,yes_core_module,source_metadata_curated_generated