metadata/sources.csv

source_id,title,year,source_type,doi_or_url,license_or_access,source_role,modality_focus,hepatotoxicity_relevance,use_in_core_dataset,notes,record_origin,original_pdf_redistributed,license_for_generated_output
MEMO_OLIGOTOX_PHASE2_ALIGNMENT,DBbun OligoTox Phase 2 Alignment Memo,2026,alignment_memo,internal_db_bun_alignment_memo,DBbun-authored working memo,governing_schema_and_rules,ASO|gapmer|siRNA|GalNAc-siRNA,governing,yes,"Defines target tables, predictors, controls, provenance, and generation rules.",source_metadata,no,CC BY 4.0
PNPLA3_ROMEO_VALENTI_2025,Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics,2025,review_open_access,10.1111/liv.70240,Creative Commons Attribution,PNPLA3_precision_genetics_siRNA_ASO_therapeutic_targeting_context,siRNA|ASO,supporting_liver_genetics_MASLD_precision_therapy_context,supporting,"Adds PNPLA3 I148M genotype context, homozygous-carrier precision-therapy response logic, siRNA/ASO liver-fat reduction proxies, adiposity/insulin-resistance/sex modifiers, and hepatic lipid-droplet biology. Supporting MASLD context, not direct OligoTox hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
RAPIROSIRAN_SANYAL_2025,Phase I randomized double-blind study of an RNA interference therapeutic targeting HSD17B13 for metabolic dysfunction-associated steatohepatitis,2025,phase1_randomized_double_blind_clinical_open_access,10.1016/j.jhep.2025.05.031,CC BY 4.0,HSD17B13_GalNAc_siRNA_clinical_PK_PD_liver_safety_and_MASH_histology_context,GalNAc-siRNA|HSD17B13|rapirosiran|MASH|ALT|AST|NAS|liver_biopsy|ASGPR,directly_relevant_clinical_low_DILI_GalNAc_siRNA_liver_safety_and_hepatocyte_target_knockdown_reference,yes_core_clinical_PK_PD_safety_module,"Strengthened from uploaded paper: phase I randomized double-blind rapirosiran study in healthy adults and MASH; subcutaneous GalNAc-siRNA, Q12W x2 dosing in MASH, dose-dependent liver HSD17B13 mRNA reduction, no evidence of drug-induced liver injury, ALT/AST numerical decreases, biopsy-derived NAS context, rapid plasma PK with prolonged liver PD.",source_metadata,no,CC BY 4.0
LIVER_SPHEROID_SCHOLTEN_2026,A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs,2026,human_in_vitro_open_access,10.1111/cts.70536,Creative Commons Attribution,human_liver_spheroid_GalNAc_siRNA_screening,GalNAc-siRNA,human_liver_model_and_no_observed_toxicity_context,yes,"Adds long-term human liver spheroid model, GalNAc uptake, durability, PS backbone variation, and human-relevant in vitro context.",source_metadata,no,CC BY 4.0
RO7239958_GERETTI_2025,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",2025,phase1_clinical_open_access,10.1128/aac.00679-25,CC BY 4.0,ASO_safety_PK_PD_transaminase_reference,GalNAc-LNA-ASO,clinical_transaminase_and_narrow_window_context,yes,"Adds ASO clinical safety, PK/PD, liver uptake saturation concept, and transaminase-related toxicity signals.",source_metadata,no,CC BY 4.0
MOHAMED_NANOPARTICLE_HEPATITIS_2026,Nanoparticle approaches for hepatitis therapy and clinical translation,2026,review_open_access_restricted_reuse,10.1186/s11671-026-04450-8,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,nanoparticle_delivery_hepatic_targeting_and_safety_context,siRNA|ASO|RNAi|nanocarrier_delivery,delivery_related_hepatic_targeting_immunogenicity_and_nanocarrier_toxicity_context,supporting_context_only,"Adds nanoparticle delivery variables: carrier type, size, zeta potential, PEGylation, ligand targeting, ASGPR/galactose targeting, Kupffer clearance, immunogenicity, oxidative stress, and delivery-related toxicity modifiers. Source PDF is not redistributed.",source_metadata,no,CC BY 4.0
MENG_HYBRID_RNA_LNP_HCC_2025,Reversal of tumour immune evasion via enhanced MHC-Class-I antigen presentation by a dual-functional RNA regulated system,2025,research_open_access_restricted_reuse,10.1186/s12943-025-02480-x,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,hybrid_RNA_LNP_payload_architecture_and_liver_tumour_immunomodulation_context,siRNA|mRNA|hybrid_RNA_LNP|PCSK9_siRNA,supporting_delivery_payload_and_immune_activation_context_not_direct_oligotox_hepatotoxicity,supporting_context_only,"Adds hybrid RNA payload variables: fluorinated LNP context, siRNA+mRNA co-delivery, PCSK9 knockdown, MHC-I/antigen-presentation enhancement, and immune-activation context. Source PDF is not redistributed.",source_metadata,no,CC BY 4.0
CHEN_OVARIAN_MTTP_APOB_MIPOMERSEN_2025,Ovarian expression of functional MTTP and apoB for VLDL assembly and secretion in chickens,2025,research_open_access,10.1016/j.psj.2025.104993,CC BY 4.0,APOB_ASO_mipomersen_lipid_export_and_lipotoxic_stress_context,ASO|Mipomersen|APOB|MTTP|VLDL_secretion,supporting_lipid_homeostasis_and_APOB_ASO_context_not_direct_hepatotoxicity,supporting_context_only,"Adds ApoB/MTTP/VLDL lipid-export variables and Mipomersen-like APOB ASO context. The source is chicken ovarian biology, so it is used only as supporting lipid-homeostasis evidence, not as direct liver toxicity evidence.",source_metadata,no,CC BY 4.0
LU_SULT1B1_SE_MASLD_2026,Super-enhancer-driven recruitment of C/EBPbeta by SULT1B1 is implicated in metabolic dysfunction-associated steatotic liver disease progression,2026,research_open_access_restricted_reuse_article_in_press,10.1186/s13148-026-02121-0,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,MASLD_epigenetic_lipid_accumulation_SULT1B1_CEBPB_siRNA_context,siRNA|SULT1B1|CEBPB|hepatocyte_lipid_accumulation|H3K27ac|JQ1,supporting_liver_disease_lipid_accumulation_and_siRNA_knockdown_context_not_direct_oligotox_toxicity,supporting_context_only,"Adds hepatocyte MASLD epigenetic/lipid-accumulation variables: H3K27ac/super-enhancer activity, CEBPB-SULT1B1 axis, oleate challenge, JQ1-like SE inhibition, and SULT1B1/CEBPB siRNA knockdown context. Source PDF is not redistributed.",source_metadata,no,CC BY 4.0
OOSTVEEN_ANGPTL3_LIVER_SAFETY_2023,Angiopoietin-like 3 inhibition and the liver: less is more?,2023,review_open_access,10.1097/MOL.0000000000000898,CC BY 4.0,ANGPTL3_ASO_vs_siRNA_liver_safety_and_hepatic_fat_context,GalNAc-ASO|GalNAc-siRNA|ANGPTL3|vupanorsen|ARO-ANG3|ALT_AST|hepatic_fat_fraction,directly_relevant_platform_specific_liver_safety_signal_for_ANGPTL3_oligonucleotides,yes_supporting_direct_liver_safety_module,Adds ANGPTL3 liver-safety variables contrasting high-inhibition GalNAc-ASO/vupanorsen-like transaminase and hepatic-fat signals with ARO-ANG3-like siRNA liver-safety/fat-reduction context. Source article is open access CC BY 4.0.,source_metadata,no,CC BY 4.0
ENGELBEEN_ALK4_MUSCLE_SIRNA_2023,Efficient Downregulation of Alk4 in Skeletal Muscle After Systemic Treatment with Conjugated siRNAs in a Mouse Model for Duchenne Muscular Dystrophy,2023,research_open_access,10.1089/nat.2022.0021,CC BY 4.0,cholesterol_conjugated_siRNA_extrahepatic_delivery_tolerability_context,cholesterol-conjugated_siRNA|ALK4|skeletal_muscle|mdx_mouse|extrahepatic_delivery,supporting_extrahepatic_delivery_and_systemic_tolerability_context_not_direct_hepatotoxicity,supporting_context_only,"Adds chemically modified cholesterol-conjugated siRNA delivery context: 2prime-F/2prime-OMe modifications, phosphorothioate linkages, cholesterol ligand, IP/IV systemic dosing, skeletal-muscle/diaphragm/liver knockdown proxies, and liver/kidney tolerability markers. Used as supporting delivery-platform context, not direct OligoTox hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
KIM_MILASEN_CUSTOM_ASO_2019,Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease,2019,n_of_1_clinical_brief_report,10.1056/NEJMoa1813279,NEJM copyrighted article; use as evidence/context only; do not reproduce source figures/tables/text,patient_customized_splice_modulating_ASO_design_safety_workflow_context,splice-switching_ASO|2prime-MOE|phosphorothioate|intrathecal|offtarget_screen|N-of-1,supporting_ASO_design_and_safety_workflow_context_not_direct_hepatotoxicity,supporting_context_only,"Adds personalized ASO workflow variables: patient-specific variant/splice defect, ASO screening, 22-nt phosphorothioate/2prime-MOE chemistry, off-target screen, fibroblast splice/functional rescue, intrathecal dosing, rat toxicology dose-escalation, CSF PK, and N-of-1 monitoring. Used as platform/workflow context only, not liver toxicity evidence.",source_metadata,no,CC BY 4.0
KEATING_ASO_OBESITY_NAFLD_2022,Antisense Oligonucleotide Technologies to Combat Obesity and Fatty Liver Disease,2022,mini_review_open_access,10.3389/fphys.2022.839471,CC BY 4.0,ASO_metabolic_NAFLD_targeting_delivery_chemistry_and_hepatotoxicity_challenges_context,ASO|gapmer|GalNAc-ASO|NAFLD|obesity|DNL|RNase_H1|hepatotoxicity|offtarget|IFN_response,directly_relevant_review_context_for_ASO_liver_uptake_hepatic_injury_offtarget_sequence_motifs_and_metabolic_NAFLD_targets,yes_supporting_ASO_metabolic_safety_module,"Adds ASO/NAFLD metabolic target context, GalNAc hepatocyte targeting, RNase-H1 gapmer mechanism, DNL/lipid-partitioning targets, ALT/AST/GGT hepatic-injury monitoring, sequence-motif toxicity, kidney-injury context, and type-I-interferon off-target response variables.",source_metadata,no,CC BY 4.0
HAGEDORN_LNA_HEPATOTOX_RF_2013,Hepatotoxic Potential of Therapeutic Oligonucleotides Can Be Predicted from Their Sequence and Modification Pattern,2013,research_open_access,10.1089/nat.2013.0436,Mary Ann Liebert open-access article; use as evidence/context only; do not reproduce source figures/tables/text,sequence_modification_pattern_hepatotoxicity_prediction_context,LNA_gapmer|phosphorothioate_ASO|RNase_H|sequence_motif|ALT|histopathology|random_forest_classifier,directly_relevant_sequence_and_modification_based_hepatotoxicity_prediction_for_therapeutic_oligonucleotides,yes_sequence_modification_toxicity_module,"Adds LNA/PS gapmer sequence-toxicity variables: dinucleotide feature encoding, ALT-based low/high toxicity classes, random-forest style prediction context, edit-distance confidence, and redesign-to-lower-toxicity logic. Source article is used as scientific context only.",source_metadata,no,CC BY 4.0
GANE_VIR2218_ALNHBV_HBV_RNAI_2023,Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials,2023,preclinical_and_randomized_clinical_open_access_restricted_reuse,10.1016/j.jhep.2023.05.023,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt source figures/tables/text,GalNAc_siRNA_ESCplus_seed_region_offtarget_and_ALT_safety_context,GalNAc-siRNA|ESCplus|glycol_nucleic_acid|seed_region|HBV_X|ALT|HBsAg,directly_relevant_siRNA_sequence_modification_safety_and_clinical_ALT_context,yes_supporting_RNAi_sequence_safety_module,"Adds VIR-2218 vs ALN-HBV comparison: identical HBV-targeting siRNA sequence except ESC+ glycol nucleic acid seed-region modification, reduced seed-mediated off-target effects, lower ALT elevations in humanized mice and healthy volunteers, and dose-dependent HBsAg reduction in cHBV participants. Source PDF is not redistributed.",source_metadata,no,CC BY 4.0
DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,Zilebesiran—Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension,2025,review_open_access,10.3390/jcm14207365,CC BY 4.0,zilebesiran_GalNAc_siRNA_AGT_RAAS_blood_pressure_durability_and_safety_monitoring_context,GalNAc-siRNA|AGT|angiotensinogen|RAAS|hypertension|ASGPR|RISC|endosomal_depot,supporting_clinical_GalNAc_siRNA_hepatocyte_targeting_and_systemic_safety_monitoring_context_not_direct_hepatotoxicity,supporting_context_only,"Adds zilebesiran-like AGT siRNA variables: GalNAc-ASGPR hepatocyte delivery, RISC-mediated AGT mRNA degradation, prolonged endosomal-depot PD, serum angiotensinogen reduction, blood-pressure reduction, six-month dosing context, hyperkalemia/hypotension/eGFR monitoring, RAAS suppression, and reversibility/rescue context. Used as supporting platform and safety-monitoring evidence, not direct oligonucleotide-induced hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
HAUPTMANN_SIRNA_BULGES_GALNAC_2022,Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression,2022,mechanistic_siRNA_design_open_access_restricted_reuse,10.1016/j.omtn.2022.02.004,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,guide_strand_bulge_tolerance_GalNAc_siRNA_offtarget_prediction_context,siRNA|GalNAc-siRNA|modified_siRNA|guide_strand_bulge|off_target_prediction,supporting_offtarget_design_context_not_direct_hepatotoxicity,supporting_context_only,"Adds siRNA guide-strand bulge features: passenger-strand-shortening design, 1-2 nt bulge tolerance, seed-region activity loss, terminal guide-target degeneracy/off-target repression, GalNAc-siRNA receptor-mediated uptake, TTR in vivo activity, and off-target prediction with nucleotide omissions.",source_metadata,no,CC BY 4.0
XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,Integrated Multi-Omics and Spatial Transcriptomics Identify FBLL1 as a Malignant Transformation Driver in Hepatocellular Carcinoma,2026,HCC_multiomics_spatial_transcriptomics_functional_siRNA_open_access,10.3390/cells15030246,CC BY 4.0,FBLL1_HCC_malignant_hepatocyte_spatial_context_and_siRNA_knockdown_growth_suppression_context,research_siRNA|FBLL1|HCC|spatial_transcriptomics|single_cell_RNAseq|EGFR_MAPK|c_Myc|hepatocyte_dedifferentiation,supporting_liver_cancer_malignant_state_and_siRNA_design_context_not_direct_oligonucleotide_hepatotoxicity,supporting_context_only,"Adds FBLL1/HCC context variables: malignant hepatocyte spatial enrichment, tumor-niche expression, siRNA-mediated knockdown suppression of HCC proliferation/colonies, overexpression-driven tumorigenesis, ALB downregulation, c-Myc/EGFR-ligand/MAPK activation, and HCC context confidence. Used as liver disease and RNAi functional-context evidence, not as direct therapeutic oligonucleotide hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,Dual targeted gene delivery strategy mediated by GalNAc-modified lipid nanoparticles enhances liver regeneration through specific knockdown of MKK4,2026,GalNAc_LNP_siRNA_liver_regeneration_open_access,10.1016/j.mtbio.2026.103059,CC BY 4.0,GalNAc_modified_LNP_siMKK4_hepatocyte_targeting_liver_regeneration_ACLF_context,GalNAc-LNP-siRNA|siMKK4|MKK4|ASGPR|hepatocyte_targeting|liver_regeneration|ACLF,supporting_hepatocyte_delivery_biocompatibility_liver_injury_regeneration_and_function_recovery_context_not_direct_oligotox_hepatotoxicity,supporting_delivery_and_liver_regeneration_module,"Adds dual-targeted GalNAc-LNP delivery variables: DOTAP/DSPC/cholesterol/GalNAc-PEG2000-DSPE composition, N/P ratio, particle size, zeta, PDI, encapsulation efficiency, RNase protection, ASGPR hepatocyte targeting, AML-12 CCl4 injury rescue, MKK4-p38 downregulation, MKK7-JNK/ATF2/ELK1 regeneration signaling, hemolysis/cytotoxicity, liver distribution, and ACLF/partial-hepatectomy regeneration context.",source_metadata,no,CC BY 4.0
WANG_OGT_SEV_LSEC_MASLD_2026,OGT-enriched Hepatocyte-derived Extracellular Vesicles Promote Capillarization of Liver Sinusoidal Endothelial Cells in Metabolic Dysfunction-associated Steatotic Liver Disease,2026,research_open_access_restricted_reuse,10.1016/j.jcmgh.2025.101721,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,MASLD_LSEC_capillarization_extracellular_vesicle_OGT_HNF1A_Ang2_context,hepatocyte_derived_sEV|OGT|LSEC|MASLD|Ang-2|BAGN,supporting_liver_microenvironment_ALT_AST_MASLD_progression_context_not_direct_oligo_toxicity,supporting_context_only,"Adds OGT-enriched lipotoxic hepatocyte-derived sEVs, LSEC capillarization/defenestration, HNF1a Ser471 O-GlcNAcylation, Ang-2 activation, serum/sEV OGT biomarker behavior, ALT/AST correlation, and BAGN rescue variables. Source PDF is not redistributed.",source_metadata,no,CC BY 4.0
DU_MALAT1_HBV_HCC_ASO_2025,MALAT1 promotes malignancy of HBV-related hepatocellular carcinoma by regulating IGF2BP3-mediated nuclear-cytoplasmic shuttling,2025,research_open_access,10.7150/ijbs.112133,CC BY 4.0; use as evidence/context; original article not redistributed,HBV_HBx_MALAT1_m6A_IGF2BP3_ASO_intervention_context,ASO|lncRNA|HBV_HCC|m6A_epigenetic_RNA_context,supporting_HBV_HCC_liver_disease_ASO_intervention_and_epigenetic_context_not_direct_oligotox_hepatotoxicity,supporting_context_only,"Adds HBx-induced MALAT1, METTL3/METTL14/WTAP m6A modification, IGF2BP3-mediated nuclear-cytoplasmic shuttling/stabilization, ASO-MALAT1 tumor suppression, and HBV-related HCC context. Not treated as direct oligonucleotide hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
PAN_CD133_MASLD_HCC_SIRNA_2025,Targeting cancer stem cells enhances multikinase inhibitor therapy in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma,2025,research_open_access_restricted_commercial_reuse,10.1136/gutjnl-2025-336527,CC BY-NC; use as evidence/context; original article not redistributed,MASLD_HCC_CD133_CSC_VNP_siRNA_multikinase_inhibitor_resistance_context,siRNA|nanoparticle_siRNA|CD133_PROM1|sorafenib|lenvatinib|MASLD_HCC,supporting_MASLD_HCC_liver_disease_siRNA_therapeutic_context_not_direct_oligotox_hepatotoxicity,supporting_context_only,"Adds CD133-positive cancer stem cell enrichment, lineage expansion, MYH9/Wnt/beta-catenin mechanism, multikinase inhibitor resistance, and VNP-siCD133 combination-treatment context in MASLD-HCC. Not treated as direct oligonucleotide hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases,2025,research_open_access_restricted_commercial_reuse,10.2147/IJN.S510937,CC BY-NC; use as evidence/context; original article not redistributed,GalNAc_RBC_EV_hepatocyte_delivery_ASO_siRNA_PJ34_ALF_NAFLD_HCC_context,GalNAc-RBC-EV|ASO|siRNA|miR-155-ASO|Rab7-siRNA|PJ34|ASGPR|hepatocyte_delivery,supporting_liver_targeted_oligonucleotide_delivery_safety_ALT_AST_context,yes_supporting_delivery_context,"Adds GalNAc-modified RBC-derived EVs for ASGPR-mediated hepatocyte uptake, RBC-EVs/GalNAc-miR-155-ASO in acute liver failure, GalNAc-RBC-EVs/PJ34 in NAFLD, and RBC-EVs/GalNAc-Rab7-siRNA/PJ34 in HCC. Encodes delivery, uptake, ALT/AST, PANoptosis, PARP-1, drug-retention, and biosafety context; not treated as direct oligo intrinsic sequence-toxicity evidence.",source_metadata,no,CC BY 4.0
KARTOUN_MELD_PLUS_CIRRHOSIS_2017,The MELD-Plus: A generalizable prediction risk score in cirrhosis,2017,clinical_prediction_model_open_access,10.1371/journal.pone.0186301,CC BY 4.0,clinical_liver_severity_cirrhosis_mortality_risk_score_context,clinical-risk-score|EMR|cirrhosis|MELD-Plus|albumin|bilirubin|creatinine|INR|sodium|WBC|cholesterol|age|length-of-stay,supporting_clinical_liver_severity_and_outcome_stratification_context_not_direct_oligo_toxicity,supporting_context_only,"Adds a clinical liver-severity and outcome-risk context module based on MELD-Plus, a 9-variable EMR-derived cirrhosis post-discharge mortality model. Useful for mapping generated hepatotoxicity/liver-injury signals to clinical liver-severity context; not direct oligonucleotide intrinsic toxicity evidence.",source_metadata,no,CC BY 4.0
MA_FORMONONETIN_ALDH2_ALD_2025,Formononetin mitigates alcoholic liver disease by restoring ALDH2 function and inducing ERK1/2–Nrf2 antioxidant signaling,2025,research_article_supporting_liver_context,https://doi.org/10.1016/j.phymed.2025.157408,open_access_CC_BY_NC_ND,supporting_liver_context,small_molecule_hepatoprotective_context_with_siRNA_validation,supporting_aldehyde_detoxification_oxidative_stress_mitochondrial_liver_context,supporting,"ALDH2 activity, acetaldehyde detoxification, ROS/lipid peroxidation, mitochondrial function, ERK1/2-Nrf2 antioxidant signaling, and AAV8 siRNA loss-of-rescue controls.",source_metadata,no,CC BY 4.0
VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,In Vivo HOXB7 Gene Silencing and Cotreatment with Tamoxifen for Luminal A Breast Cancer Therapy,2024,research_article_supporting_siRNA_nanoparticle_safety_context,https://doi.org/10.3390/ph17101325,open_access_CC_BY,supporting_delivery_platform_safety_context,calcium_phosphate_hybrid_nanoparticle_siRNA,supporting_delivery_platform_safety_and_systemic_siRNA_context,supporting,Calcium phosphate/PEG-pGlu hybrid nanoparticles delivering HOXB7 siRNA; pH-responsive destabilization/endosomal escape context; no hemolysis; in vivo tumor HOXB7 knockdown and tamoxifen cotreatment with ALT/AST safety monitoring.,source_metadata,no,CC BY 4.0
WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,Robust loading and delivery of functional small RNAs via protein N-myristoylation-induced small extracellular vesicles,2026,research_article_supporting_sEV_small_RNA_delivery_context,https://doi.org/10.1016/j.bioactmat.2026.04.012,open_access_CC_BY,supporting_sEV_RNA_delivery_and_hepatic_safety_context,engineered_small_extracellular_vesicle_siRNA_miRNA_delivery,supporting_sEV_RNA_loading_hepatocyte_delivery_and_systemic_safety_context,supporting,"PMEVL uses N-myristoylation peptides to load siRNAs/miRNAs/mRNAs into sEVs; mechanism includes ERK1/2 activation, AMPK-autophagy inhibition, ANXA2, ALIX, TSG101, AGO2; Pcsk9 siRNA-loaded sEVs accumulate in liver, suppress hepatic Pcsk9, restore LDLR, lower LDL-C/total cholesterol, and show normal ALT/AST and H&E safety context.",source_metadata,no,CC BY 4.0
ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,Preclinical Safety Assessment of Therapeutic Oligonucleotides,2022,methods_chapter_preclinical_safety_review,10.1007/978-1-0716-2010-6_25,NCBI_Bookshelf_methods_chapter_context_only,direct_preclinical_oligonucleotide_safety_framework,ASO|siRNA|miRNA_mimic|GalNAc|LNP|PS_gapmer,direct_preclinical_liver_kidney_immunotoxicity_offtarget_safety_context,yes,"Used to strengthen safety-assessment variables, controls, and provenance; source text/figures are not redistributed.",source_metadata,no,CC BY 4.0
BI_IFNA_DISULFIDPTOSIS_HCC_2026,Interferon-alpha induces disulfidptosis occurrence in human liver cancer cells,2026,mechanistic_cell_study_liver_cancer,10.3760/cma.j.cn501113-20250612-00233,journal_pdf_user_provided; use as evidence/context only; do not reproduce source figures/tables/text,IFN_alpha_HCC_disulfidptosis_NADPH_Factin_SLC7A11_context,IFN-alpha|HepG2|Huh7|disulfidptosis|SLC7A11_siRNA|NADPH|F-actin|D-penicillamine|B2M|USP18|PSME1,supporting_human_liver_cancer_cell_disulfide_stress_and_noncanonical_cell_death_context_not_direct_therapeutic_oligo_hepatotoxicity,supporting_context_only,"Adds IFN-alpha induced disulfidptosis context in HepG2/Huh7 cells: high-molecular-weight disulfide-linked protein aggregation, NADPH depletion, F-actin collapse, partial D-penicillamine rescue, SLC7A11 knockdown aggravation, and candidate interferon-stimulated genes B2M/USP18/PSME1.",source_metadata,no,CC BY 4.0
JANAS_GALNAC_RNAI_NONCLINICAL_SAFETY_2018,The Nonclinical Safety Profile of GalNAc-conjugated RNAi Therapeutics in Subacute Studies,2018,review_platform_nonclinical_safety,10.1177/0192623318792537,SAGE article user_provided; use as evidence/context only; do not reproduce source figures/tables/text,GalNAc_siRNA_ESC_nonclinical_safety_platform_rat_monkey_liver_kidney_RES_context,GalNAc-siRNA|ESC chemistry|ASGPR|RISC|rat|cynomolgus monkey|liver|kidney|reticuloendothelial system|seed off-target hepatotoxicity,directly_relevant_GalNAc_siRNA_nonclinical_safety_and_liver_toxicity_platform_context,yes_core_GalNAc_siRNA_safety_module,"Adds platform-level nonclinical safety logic for ESC GalNAc-siRNAs: ASGPR hepatocyte uptake, low extrahepatic distribution, exaggerated-dose rat/monkey toxicology, liver/kidney/RES findings, mostly nonadverse/reversible accumulation-related changes, genotoxicity/safety-pharmacology negatives, and seed-region mediated off-target hepatotoxicity screening.",source_metadata,no,CC BY 4.0
BOSCO_INCLISIRAN_FH_REALWORLD_2025,Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience,2025,clinical_real_world_observational_inclisiran,10.1016/j.pcad.2025.05.008,CC BY 4.0,inclisiran_PCSK9_GalNAc_siRNA_real_world_FH_lipid_PWV_ALT_AST_safety_context,inclisiran|PCSK9|GalNAc-siRNA|LDL-C|LDLR|familial hypercholesterolemia|PWV|ALT|AST|CPK,supporting_clinical_GalNAc_siRNA_tolerability_and_liver_enzyme_monitoring_context_not_hepatotoxicity_mechanism,supporting_clinical_PCSK9_GalNAc_siRNA_context,"Adds real-world clinical inclisiran context: 284 mg dosing, six-month LDL-C/ApoB/non-HDL-C/Lp(a) reduction, PWV improvement, PCSK9 hepatic mRNA silencing/LDLR expression mechanism, and stable liver/muscle enzyme monitoring.",source_metadata,no,CC BY 4.0
DEBACKER_GALNAC_LIVER_DELIVERY_REVIEW_2020,Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug,2020,review_GalNAc_liver_delivery_clinical_translation,10.1016/j.ymthe.2020.06.015,CC BY 4.0,GalNAc_ASGPR_hepatocyte_delivery_ASO_siRNA_clinical_translation_and_safety_context,GalNAc|ASGPR|hepatocyte|siRNA|ASO|GalNAc-ASO|GalNAc-siRNA|endosomal_escape|ESC|ESCplus|Reversir|givosiran|inclisiran|clinical_pipeline,directly_relevant_delivery_and_safety_context_for_liver_targeted_therapeutic_oligonucleotides,yes_core_GalNAc_liver_delivery_module,"Adds broad GalNAc liver-delivery framework: ASGPR-mediated hepatocyte targeting, ASO hepatocyte uptake shift, 10-30 fold ASO potency improvement, GalNAc-siRNA replacement of LNP for liver targets, ESC/ESC+ seed-region safety mitigation, Reversir reversal concept, ASGPR saturation/kidney distribution, and clinical pipeline/registered-drug context.",source_metadata,no,CC BY 4.0
RANASINGHE_SIRNA_PHARMACOLOGY_REVIEW_2023,"Small interfering RNA: Discovery, pharmacology and clinical development — An introductory review",2023,review_siRNA_discovery_pharmacology_clinical_development,10.1111/bph.15972,CC BY open access; user-provided PDF; cite source but do not reproduce full tables/figures/text,siRNA_mechanism_pharmacology_delivery_clinical_landscape_context,siRNA|RISC|AGO2|seed_region|GalNAc-siRNA|LNP|chemical_modification|immune_activation|off-target|approved_siRNA_drugs,supporting_core_siRNA_pharmacology_and_liver_delivery_context_for_OligoTox_interpretation,yes_core_siRNA_pharmacology_context,"Adds introductory siRNA mechanism and translational context: RISC/AGO2 loading, guide/passenger strand logic, seed/central/supplementary regions, PK/PD barriers, nuclease and renal clearance, immune activation/off-target effects, chemical modifications, GalNAc delivery, LNP delivery, and approved/developing siRNA therapeutics.",source_metadata,no,CC BY 4.0
KAMOLA_ASO_HEPATOTOX_SCREEN_2017,Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs,2017,peer_reviewed_open_access_article,10.1016/j.omtn.2017.07.003,CC BY-NC-ND 4.0,ASO_gapmer_hepatotoxicity_screening_offtarget_mitigation,LNA_gapmer_ASO,core_hepatotoxicity_screening_positive_negative_controls,yes,"Adds positive/negative ASO gapmer controls, acute 3-day screen proxies, repeat-dose concordance, OTE count, transcriptome selectivity, ALT/AST and liver-weight endpoints.",source_metadata,no,CC BY 4.0
LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism,2025,bioRxiv_preprint_not_peer_reviewed,10.1101/2025.05.01.651783,bioRxiv preprint; author/funder copyright notice says no reuse without permission; use as evidence/context only; do not redistribute source text or figures,LNP_delivered_LNA_gapmer_AGO1_ASO_liver_function_vascular_inflammation_context,LNP-ASO|LNA_gapmer_ASO|AGO1|endothelial_cell|liver_function|ALT_AST,supporting_ASO_delivery_liver_function_no_evident_hepatotoxicity_and_inflammation_context,supporting_context_with_preprint_caution,"Adds endothelial AGO1/NF-kB inflammatory mechanism, EC-hepatocyte paracrine metabolic context, LNP-ASO formulation variables, hyperlipidemia/atherosclerosis model context, and low ALT/AST/no-evident-hepatotoxicity safety-monitoring controls. Treated as preprint/supporting context, not definitive direct OligoTox evidence.",source_metadata,no,CC BY 4.0
WEISS_GYS1_ASO_POMPE_PREPRINT_2024,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,2024,bioRxiv_preprint_not_peer_reviewed,10.1101/2024.02.22.580414,bioRxiv preprint; author/funder copyright notice says no reuse without permission; use as evidence/context only; do not redistribute source text or figures,supporting_extrahepatic_ASO_gapmer_safety_and_ALT_AST_monitoring_context,ASO|RNase_H1_gapmer|cEt|phosphorothioate|subcutaneous|GYS1|Pompe|ERT_combination,supporting_systemic_ASO_tolerability_context_with_ALT_AST_BUN_CK_and_organ_weight_monitoring,supporting_context_with_preprint_caution,"Adds systemic extrahepatic ASO safety/tolerability context: 16-mer PS cEt 3-10-3 gapmer, weekly subcutaneous dosing, Gys1 knockdown in muscle/heart, combination with ERT, no significant elevation in liver transaminases, BUN, or CK in the described context. Treated as supporting preprint context, not direct oligonucleotide hepatotoxicity evidence.",source_metadata,no,CC BY 4.0
OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,Dynamic cholangiocyte responses in a murine model of reversible cholestasis: macrophage remodeling and NF-Y-mediated TGFβ1 expression,2025,peer_reviewed_research_article,10.1152/ajpgi.00243.2025,Creative Commons Attribution CC-BY 4.0; use as source evidence/context only; do not redistribute source PDF/figures in generated package,supporting_cholestatic_liver_injury_cholangiocyte_macrophage_fibrosis_context,cholestasis|cholangiocyte|CX3CL1_CX3CR1|macrophage|NFY|TGFB1|ALT_ALP_bilirubin|fibrosis|siRNA_NFYA_context,supporting_hepatobiliary_injury_and_fibrosis_context_with_ALT_ALP_bilirubin_cholesterol_recovery_endpoints,supporting_liver_pathobiology_context_not_direct_oligo_toxicity,"Adds cholestatic hepatobiliary injury and recovery context; not direct oligonucleotide hepatotoxicity evidence, but useful for ALT/ALP/bilirubin/fibrosis/cholangiocyte inflammatory-response variables and a mechanistic siRNA NF-YA/TGFβ1 validation context.",source_metadata,no,CC BY 4.0
KANDA_PCDHA11_AMNA_ASO_2024,Dual-modified antisense oligonucleotides targeting oncogenic protocadherin to treat gastric cancer,2024,peer_reviewed_preclinical_therapeutic_ASO_study,10.1038/s41416-024-02859-5,"Springer Nature exclusive licence; use as source evidence/context only; do not redistribute source PDF, figures, tables, sequences, or long source text",direct_preclinical_AmNA_modified_PCDHA11_ASO_sequence_dependent_reversible_hepatotoxicity_evidence,AmNA_modified_ASO|phosphorothioate|PCDHA11|gastric_cancer|mouse_toxicology|ALT_AST_ALP|bilirubin|renal_markers|offtarget_screening,direct_preclinical_oligonucleotide_liver_toxicity_evidence_with_dose_sequence_dependence_and_reversibility,yes_direct_hepatotoxicity_module,"Adds a direct AmNA-ASO hepatotoxicity module. Generated values are synthetic proxies based on reported experimental structure and directionality; no source figures, source tables, source sequences, or animal-level data are redistributed.",source_metadata,no,CC BY 4.0
HJELMGREN_PS_ASO_DDR_2026,Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides,2026,mechanistic_ASO_toxicity_open_access,10.1038/s41467-026-69980-2,Nature Communications open-access article; use as evidence/context only; do not reproduce source figures/tables/text,PS_ASO_DNA_damage_response_phase_separation_toxicity_mechanism,phosphorothioate_ASO|LNA_gapmer|PS_body|DNA-PKcs|ATM|ATR|PARP1|DNA_damage_response,direct_oligonucleotide_toxicity_mechanism_not_liver_specific,yes_direct_mechanistic_toxicity_module,"Adds concentration-dependent PS-ASO nuclear condensate/PS-body variables, repair-enzyme binding/activation, checkpoint activation, homologous-recombination suppression, toxic DNA-lesion accumulation, and PS-vs-PO backbone contrast. Generated values are proxies and do not copy source figures or tables.",source_metadata,no,CC BY 4.0
LAN_SIRUBICON_ROS_GALNAC_MASH_2025,Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis,2025,preclinical_liver_siRNA_delivery_open_access,10.1038/s41467-025-61965-x,Nature Communications open-access article; use as evidence/context only; do not reproduce source figures/tables/text,ROS_responsive_GalNAc_hepatocyte_siRNA_delivery_MASH_lipophagy_safety_context,siRNA|GalNAc|ASGPR|ROS-responsive_nanoparticle|PEI|MASH|Rubicon|lipophagy|ALT_AST,supporting_liver_targeted_siRNA_delivery_and_disease_context_with_liver_function_readouts,yes_supporting_delivery_liver_function_module,"Adds MASH oxidative-stress triggered shell-disassembly, GalNAc/ASGPR hepatocyte targeting, Rubicon knockdown, lipophagy activation, steatosis reduction, ALT/AST/albumin liver-function context, and PEI/nanocarrier safety-monitoring variables.",source_metadata,no,CC BY 4.0
YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,"Cycloalkane Incorporation Into the 2′,4′-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides",2025,ASO_chemistry_hepatotoxicity_open_access,10.1021/jacsau.5c01005,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,scpBNA_scpBNA2_gapmer_ASO_chemistry_reduced_PS_lower_hepatotoxicity,gapmer_ASO|LNA|BNA|scpBNA|scpBNA2|phosphorothioate_reduction|ALT_AST|nuclease_stability,direct_ASO_chemistry_hepatotoxicity_reduction_evidence,yes_direct_chemistry_safety_module,"Adds generated chemistry-safety variables for scpBNA/scpBNA2 substitution, reduced PS burden, retained knockdown, nuclease stability, and lower ALT/AST.",source_metadata,no,CC BY 4.0
LIU_CYP2E1_LNP_APAP_AILI_2025,Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo,2025,preclinical_RNAi_LNP_DILI_open_access,10.3390/cimb47050372,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,siCyp2e1_LNP_APAP_acute_liver_injury_ALT_AST_oxidative_stress_inflammation_recovery,siRNA|LNP|CYP2E1|APAP|DILI|ALT_AST|ROS|MDA|SOD|GSH|PPAR|IL6_IL1B_TNFA,direct_liver_injury_RNAi_intervention_and_readout_context,yes_direct_liver_injury_RNAi_module,"Adds generated APAP acute liver injury context, si-Cyp2e1 LNP knockdown, timing, ALT/AST, necrosis, oxidative stress, inflammatory cytokines, and recovery variables.",source_metadata,no,CC BY 4.0
KIM_NANP_LIPID_LIVER_TARGETING_2026,Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting,2026,nucleic_acid_nanoparticle_delivery_open_access,10.1021/acsami.5c24581,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,NANP_lipid_functionalization_GalNAc_LDLR_SR-B1_liver_cell_type_targeting_offtarget_uptake,DNA_origami_NANP|siRNA_delivery|cholesterol_lipidation|TriGalNAc|LDLR|SR-B1|ASGPR|HepG2|LSEC|Kupffer,supporting_delivery_cell_type_targeting_offtarget_liver_distribution_context,yes_supporting_delivery_targeting_module,"Adds generated NANP design variables for ligand valency, lipid chemistry, ApoE/LDLR/SR-B1 engagement, hepatocyte uptake, LSEC/Kupffer association, and immunotoxicity monitoring.",source_metadata,no,CC BY 4.0
SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,Design of Anti-Tumor RNA Nanoparticles and Their Inhibitory Effect on Hep3B Liver Cancer,2026,RNA_nanoparticle_liver_cancer_open_access,10.3390/biom16010045,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,self_assembling_RNA_nanoparticle_Hep3B_hTERT_BIRC5_FGFR1_multitarget_RNAi_safety_context,RNA_nanoparticle|RNAi|Hep3B|hTERT|BIRC5|FGFR1|apoptosis|migration|xenograft|offtarget_toxicity,supporting_liver_cell_RNAi_platform_safety_and_offtarget_context,yes_supporting_liver_RNAi_platform_module,"Adds generated RNA nanoparticle variables for multitarget RNAi in Hep3B cells, liver-cancer xenograft context, proliferation/migration/apoptosis, and off-target toxicity monitoring.",source_metadata,no,CC BY 4.0
MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,"Design, Screening and Development of Asymmetric siRNAs Targeting the MYC Oncogene in Triple-Negative Breast Cancer",2025,asymmetric_siRNA_design_delivery_safety_open_access_noncommercial,10.4062/biomolther.2024.071,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,asymmetric_siRNA_VP_DCA_cholesterol_extrahepatic_delivery_durable_knockdown_safety_context,asiRNA|MYC|docosanoic_acid|cholesterol|vinylphosphonate|2prime_OMe|2prime_F|PS|RRM2|RAD51|PARP1|offtarget_reduction,supporting_modification_delivery_safety_and_offtarget_design_context_not_direct_liver_toxicity,yes_supporting_siRNA_design_safety_module,"Adds generated asymmetric-siRNA design variables: reduced seed/off-target risk, DCA conjugation, VP modification, long-duration knockdown, and visible-toxicity monitoring.",source_metadata,no,CC BY 4.0
SOUSA_HDO_MULTIFUNCTIONAL_HELA_2022,Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells,2022,HDO_intracellular_delivery_open_access,10.3390/biomedicines10092096,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,heteroduplex_ASO_multifunctionalization_folate_peptide_delivery_gene_silencing_context,HDO|ASO_RNA_heteroduplex|folate|peptide|HeLa|GFP|BCL2|intracellular_delivery,supporting_delivery_design_and_gene_silencing_context_not_liver_specific,yes_supporting_delivery_design_module,"Adds generated HDO multifunctionalization variables for targeted intracellular delivery, dual ligand labeling, GFP/BCL2 silencing context, and non-liver off-target framing.",source_metadata,no,CC BY 4.0
KUMAGAI_SCPBNA2_PURINE_SYNTHESIS_2025,"Development of Synthetic Routes to 2-O,4-C-Spirocyclopentylene-Bridged Nucleic Acids: Thymidine, Guanosine, and Adenosine",2025,ASO_chemistry_synthesis_open_access,10.1002/chem.202502995,CC BY 4.0; evidence/context only; generated variables only; no source schemes reproduced,scpBNA2_full_monomer_synthesis_T_G_A_chemistry_context,scpBNA2|BNA|LNA|purine_nucleosides|ASO_chemistry|nuclease_stability,supporting_chemistry_feasibility_context_already_covered_by_direct_scpBNA2_hepatotoxicity_module,triage_deferred_context_only,Deferred from full module because v1.0 already contains the direct scpBNA/scpBNA2 hepatotoxicity evidence; this source supports chemistry feasibility rather than adding new toxicity readouts.,source_metadata,no,CC BY 4.0
BJD_BMP1_SHRNA_AAV_CCL4_FIBROSIS_CONTEXT,Protective effect of knockdown Bmp1 gene on carbon tetrachloride-induced liver fibrosis in mice,2025,shRNA_AAV_liver_fibrosis_context_user_pdf_text_extraction_limited,user_provided_pdf_bjdxxbyxb_57_4_727,user-provided PDF; text extraction limited/garbled; context only until manually reviewed,Bmp1_shRNA_AAV_CCl4_liver_fibrosis_ALT_AST_context_needs_manual_review,shRNA|AAV|Bmp1|CCl4|liver_fibrosis|ALT_AST|collagen|alpha_SMA,potential_supporting_liver_injury_RNAi_context_but_deferred_due_to_extraction_quality,triage_deferred_until_better_extraction,Deferred from code-module integration in v1.0 because extracted text was not reliable enough for rigorous source-grounded variable design.,source_metadata,no,CC BY 4.0
HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen",2025,therapeutic_siRNA_design_pharmacology_toxicology_open_access_restricted_reuse,10.1016/j.omtn.2025.102542,CC BY-NC-ND 4.0; evidence/context only; generated variables only; no source figures/tables/sequences reproduced,complete_GalNAc_siRNA_development_workflow_sequence_screening_modification_pattern_delivery_toxicology_offtarget_PKPD,GalNAc-siRNA|AGT|2prime-F|2prime-MOE|VP|PS|offtarget_screening|RNAseq_toxicology|ALT_AST|kidney_safety|monkey_PKPD|Zilebesiran_comparator,directly_relevant_liver_targeted_siRNA_toxicology_offtarget_safety_and_predictive_model_gap,yes_direct_siRNA_design_toxicology_module,"Adds a direct module for systematic siRNA development: on/off-target sequence screening, modification-pattern optimization, GalNAc hepatic delivery, RNAseq off-target/toxicology logic, ALT/AST/urea/histopathology safety, and Zilebesiran-like comparator context.",source_metadata,no,CC BY 4.0
QU_CPG_ODN_APAP_TLR9_IRG1_2025,CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway,2025,CpG_ODN_APAP_liver_injury_open_access,10.1186/s10020-025-01324-0,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,CpG_ODN_TLR9_macrophage_immunomodulation_APAP_liver_injury_IRG1_itaconate_context,CpG_ODN|ODN1826|TLR9|NF-kB|IRG1|ACOD1|itaconate|APAP|macrophage|Kupffer_cell|Nrf2|ROS|apoptosis,supporting_direct_liver_injury_immunomodulatory_oligodeoxynucleotide_module_for_APAP_context_and_macrophage_toxicology,yes_supporting_ODN_immunomodulatory_liver_injury_module,"Adds CpG ODN liver-injury context: APAP model, macrophage-mediated protection, TLR9/NF-kB/IRG1/itaconate pathway, Acod1 siRNA loss-of-mechanism signal, ROS/apoptosis/survival/ALT inflammation variables.",source_metadata,no,CC BY 4.0
PARK_ERBB2_APTAMER_PET_PK_2023,In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging,2023,aptamer_tissue_PK_PET_open_access_noncommercial,10.1111/cts.13522,CC BY-NC 4.0; generated variables only; no source figures/tables reproduced,oligonucleotide_aptamer_PET_tissue_PK_biodistribution_target_specificity_excretion_context,DNA_aptamer|ERBB2|PET|fluorine-18|complementary_oligonucleotide_platform|biodistribution|organ_PK|kidney_liver_excretion|tumor_visualization,supporting_oligonucleotide_ADME_biodistribution_and_tissue_PK_context_not_intrinsic_hepatotoxicity,yes_supporting_oligo_PK_biodistribution_module,"Adds aptamer ADME/PK table with organ distribution, liver/kidney/spleen exposure, renal/biliary excretion, PET-based Cmax/Tmax/AUC/t1/2 proxies, and target-tumor visualization context.",source_metadata,no,CC BY 4.0
XI_HCC_CHROMATIN_DGAT1_SIRNA_2025,Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma,2025,single_cell_HCC_epigenomics_siRNA_validation_open_access,10.4254/wjh.v17.i6.107329,open access; evidence/context only; generated variables only if later promoted,HCC_chromatin_accessibility_DGAT1_siRNA_functional_validation_context,siRNA|DGAT1|HCC|single_cell_ATAC|single_cell_RNA|chromatin_accessibility|tumor_stroma,context_only_liver_cancer_target_biology_not_oligo_toxicity,triage_deferred_context_only,"Deferred from v1.0 full module: useful HCC target-biology and DGAT1 siRNA validation context, but not an oligo toxicity, liver enzyme, chemical modification, or ADME/toxicology paper.",source_metadata,no,CC BY 4.0
LI_AIH_CERNA_NETWORK_2022,Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis,2022,autoimmune_hepatitis_ceRNA_network_open_access,10.1186/s12920-022-01416-4,CC BY 4.0; evidence/context only; generated variables only if later promoted,autoimmune_hepatitis_lncRNA_miRNA_mRNA_network_ALT_AST_MDA_NO_context,ceRNA|lncRNA|miRNA|mRNA|autoimmune_hepatitis|ConA|ALT_AST|MDA|NO|MAPK,context_only_liver_inflammation_network_not_oligo_therapeutic_toxicity,triage_deferred_context_only,"Deferred from v1.0 full module: useful autoimmune liver-injury network context, but not directly about therapeutic oligos, chemical modifications, delivery, or oligo toxicity.",source_metadata,no,CC BY 4.0
TERADA_BROTHERS_ASO_PNA_TOEHOLD_2023,Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry,2023,direct_ASO_hepatotoxicity_mitigation_mechanism_open_access,10.1038/s41467-023-43714-0,open access; generated variables only; no source figures/tables/sequences reproduced,BROTHERS_ASO_PNA_toehold_duplex_reduces_protein_binding_RNA_offtarget_and_ALT_hepatotoxicity,ASO|PNA|BROTHERS|BRO|LNA_gapmer|GalNAc|toehold_mediated_strand_displacement|protein_binding|hybridization_offtarget|ALT|Pcsk9,direct_high_value_ASO_hepatotoxicity_mitigation_and_offtarget_mechanism_module,yes_direct_ASO_toxicity_mitigation_module,"Adds direct variables for parent toxic ASO versus ASO/PNA BRO duplexes, PNA brother-strand length/Tm, protein-binding reduction, mismatch discrimination, on-target knockdown retention, and ALT/body-weight safety margin.",source_metadata,no,CC BY 4.0
PRAKASH_APOC3_LONG_ACTING_GALNAC_SIRNA_2025,Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia,2025,direct_GalNAc_siRNA_SAR_duration_tolerability_open_access_noncommercial,10.1093/nar/gkaf1063,CC BY-NC; generated variables only; no source figures/tables/sequences reproduced,APOC3_GalNAc_siRNA_chemical_scaffold_SAR_potency_duration_selectivity_tolerability_rodent_NHP,GalNAc-siRNA|APOC3|2prime-F|2prime-OMe|2prime-MOE|PS|VP|AGO2_RISC|duration|rodent|nonhuman_primate|plozasiran_surrogate,direct_high_value_liver_targeted_siRNA_design_duration_and_tolerability_module,yes_direct_siRNA_SAR_safety_duration_module,"Adds variables for long-acting GalNAc-siRNA chemistry scaffolds, minimized 2-F burden, potency, durability, apoC3/TG lowering, off-target/selectivity, and rodent/NHP tolerability context.",source_metadata,no,CC BY 4.0
KIM_GALNAC_SIRNA_LCMS_DPPT_2025,Differential Protein Precipitation-Based GalNAc-siRNA Sample Preparation with LC/MS Method Development Workflow in Plasma,2025,GalNAc_siRNA_bioanalysis_LCMS_method_open_access_restricted_reuse,10.1021/acs.analchem.5c01587,CC BY-NC-ND 4.0; generated variables only; no source figures/tables reproduced,GalNAc_siRNA_quantification_DPPT_LCMS_PK_TK_bioanalysis_reproducibility_context,GalNAc-siRNA|LC-MS/MS|DPPT|plasma|givosiran|lumasiran|inclisiran|vutrisiran|metabolite|LLOQ|recovery|PK,supporting_high_value_bioanalysis_PK_TK_and_open_dataset_measurement_quality_module,yes_supporting_bioanalysis_reproducibility_module,"Adds analytical rigor variables: sample-prep recovery, matrix interference, LLOQ, metabolite distinction, approved GalNAc-siRNA comparators, and rat-plasma PK support.",source_metadata,no,CC BY 4.0
UMEZU_ORAL_MIR29A_LIVER_FIBROSIS_NA_2025,Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis,2025,modified_miRNA_like_liver_fibrosis_therapy_open_access_restricted_reuse,10.1016/j.omtn.2024.102438,CC BY-NC-ND 4.0; generated variables only; no source figures/tables/sequences reproduced,oral_nuclease_resistant_miR29a_like_RNA_DNA_hybrid_LNA_PS_liver_fibrosis_COL1A1_PDGFC,modified_microRNA|miR-29a-3p|RNA-DNA_hybrid|2prime-F|LNA|PS|COL1A1|PDGFC|CCl4|liver_fibrosis|oral_delivery|no_DDS,supporting_liver_delivery_fibrosis_and_modified_nucleic_acid_safety_context,yes_supporting_liver_fibrosis_modified_NA_module,"Adds liver-fibrosis variables: oral modified nucleic acid detection in liver/GI tract, nuclease-resistant chemistry, CCl4 fibrosis, collagen/PDGFC suppression, and no-carrier delivery context.",source_metadata,no,CC BY 4.0
LU_GT_MULTI_SIRNA_HCC_2025,Development of a Dual Gene-Targeted Multi-Sirna with Branched Structure and Its Role in the Therapy of Liver Cancer,2025,branched_multi_siRNA_HCC_open_access,10.3390/ph18121844,CC BY 4.0; evidence/context only; generated variables only if later promoted,dual_gene_branched_multi_siRNA_HCC_GP73_hTERT_biosafety_context,multi-siRNA|branched_RNA|GP73|hTERT|Hep3B|Dicer|intratumoral|liver_toxicity_monitoring|IL4|IL6,supporting_liver_cancer_RNAi_biosafety_context_but_redundant_with_existing_Hep3B_RNA_nanoparticle_modules,triage_deferred_context_only,"Deferred from v1.0 full module: relevant liver-cancer RNAi/biosafety context, but partly redundant with prior Hep3B RNA nanoparticle modules and less directly useful than BROTHERS/APOC3/bioanalysis/fibrosis modules for OligoTox scoring.",source_metadata,no,CC BY 4.0
JIANG_LNP_CRISPR_HAO1_PH1_2025,Efficient and safe in vivo treatment of primary hyperoxaluria type 1 via LNP-CRISPR-Cas9-mediated glycolate oxidase disruption,2025,liver_targeted_LNP_CRISPR_Cas9_long_term_safety_open_access_restricted_text_mining,10.1016/j.ymthe.2024.10.003,open access but publisher reserves text/data mining and AI training rights; generated variables only; no source figures/tables/sequences reproduced,LNP_Cas9_mRNA_sgRNA_liver_delivery_HAO1_Hao1_PH1_urinary_oxalate_offtarget_liver_toxicity_immune_response_long_term,LNP|Cas9_mRNA|sgRNA|CRISPR|HAO1|Hao1|PH1|glycolate_oxidase|urinary_oxalate|liver_delivery|off_target|immune_response|12_month_followup,supporting_high_value_liver_targeted_nucleic_acid_delivery_and_long_term_safety_module,yes_supporting_liver_delivery_safety_module,"Added in v1.0 as a supporting module because it provides unusually useful liver-targeted nucleic-acid delivery, one-dose durability, off-target assessment, immune-response monitoring, and liver-toxicity safety context, even though it is CRISPR rather than an ASO/siRNA toxicity dataset.",source_metadata,no,CC BY 4.0
GOTFRID_PS_LNA_HIV_ASO_ACTIVITY_2026,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1,2026,PS_and_PS_LNA_ASO_activity_internalization_toxicity_open_access,10.3389/fmed.2026.1719202,CC BY; generated variables only; no source figures/tables/sequences reproduced,PS_ASO_vs_PS_LNA_ASO_internalization_cytotoxicity_antiviral_activity_cellular_uptake_vehicle_free_context,antisense_oligonucleotide|phosphothioate|LNA|HIV|MT4|cell_viability|internalization|FAM_uptake|vehicle_free_delivery|IC50,supporting_ASO_chemistry_internalization_and_cell_toxicity_context_not_liver_specific,yes_supporting_ASO_chemistry_tolerability_module,"Added in v1.0 as a supporting chemistry/tolerability module because it compares PS and PS/LNA modified oligonucleotides, cell uptake, viability, internalization, and vehicle-free delivery; not liver-specific, so it is kept as supporting context rather than a direct OligoTox module.",source_metadata,no,CC BY 4.0
XU_FGF21_MAPK1_DAIRY_KETOSIS_SIRNA_2025,FGF21-MAPK1 Imbalance Disrupts Hepatic Lipid Metabolism in Dairy Cow Ketosis,2025,bovine_liver_lipid_metabolism_siRNA_functional_context,10.3390/life15091339,CC BY 4.0; evidence/context only; generated variables only if later promoted,BHB_bovine_hepatocyte_MAPK1_siRNA_lipid_metabolism_FGF21_context,siRNA|MAPK1|FGF21|bovine_hepatocytes|BHB|lipid_accumulation|ketosis|hepatic_lipid_metabolism,context_liver_lipid_metabolism_and_siRNA_validation_but_not_oligo_toxicity_or_human_oligo_safety,triage_deferred_context_only,Deferred from v1.0 full module because it is valuable liver-lipid biology but dairy-cow ketosis is too far from therapeutic oligo toxicity and human liver-safety prediction for immediate code integration.,source_metadata,no,CC BY 4.0
ELGHAZZI_GENE_SILENCING_GI_GU_TUMORS_REVIEW_2025,"Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors",2025,review_gene_silencing_oncology_context,10.3389/fimmu.2025.1657040,CC BY; review context only,ASO_siRNA_miRNA_mechanisms_delivery_modifications_clinical_oncology_review_context,ASO|siRNA|miRNA|RNAi|RISC|RNase_H|splicing|delivery|GalNAc|LNP|cancer,review_context_not_primary_dataset_or_toxicology_module,triage_deferred_review_context_only,Deferred from v1.0 module integration because it is a review rather than source data; useful for narrative/methodology background but not for synthetic variable generation.,source_metadata,no,CC BY 4.0
YANG_PIRNA_CANCER_DIAGNOSTIC_THERAPEUTIC_REVIEW_2026,Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics,2026,review_piRNA_cancer_context,10.3389/fmolb.2026.1775335,CC BY; review context only,piRNA_PIWI_cancer_diagnostics_therapeutics_review_context,piRNA|PIWI|cancer|diagnostics|therapeutics|biomarker|LNA_antisense|nanoparticle_delivery,review_context_low_direct_fit_for_oligo_hepatotoxicity_dataset,triage_deferred_review_context_only,Deferred from v1.0 module integration because it is broader piRNA oncology review context and does not directly strengthen oligo hepatotoxicity modeling.,source_metadata,no,CC BY 4.0
SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,2022,direct_GalNAc_siRNA_offtarget_hepatotoxicity_mitigation_primary_mechanistic_translation,10.1093/nar/gkac539,CC BY-NC; generated variables only; no source figures/tables/sequences reproduced,GalNAc_siRNA_ESCplus_GNA_2_5_RNA_seed_pairing_destabilization_RNAi_offtarget_hepatotoxicity_ALT_ALN_HBV_VIR2218,GalNAc-siRNA|ESC+|GNA|2-5-RNA|seed_region|RISC|off_target|ALT|hepatotoxicity|ALN-HBV|VIR-2218|rat_safety|healthy_volunteer_ALT,direct_high_value_siRNA_seed_mediated_offtarget_hepatotoxicity_and_safety_mitigation_module,yes_direct_high_value_module,"Added in v1.0 because it directly connects GalNAc-siRNA seed-region chemistry, RNAi-mediated off-target effects, ALT hepatotoxicity, rat therapeutic window, and clinical redesign of ALN-HBV to VIR-2218. The duplicate uploaded gkac539 PDF was not added separately.",source_metadata,no,CC BY 4.0
DHARA_LNA_PHOSPHOTHIOTRIESTER_SSO_CLICK_2025,Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages,2025,modified_oligonucleotide_backbone_biophysical_splice_switching_primary_chemistry,10.1093/nar/gkaf1263,CC BY 4.0; generated variables only; no source figures/tables/sequences reproduced,LNA_phosphothiotriester_charge_neutral_backbone_click_conjugates_duplex_stability_gymnosis_splice_switching_bioactivity,LNA|phosphothiotriester|PTTE|splice_switching_oligonucleotide|charge_neutral_backbone|click_conjugate|gymnosis|duplex_stability|amino_acid_conjugate,supporting_chemistry_module_for_backbone_charge_PS_reduction_bioavailability_and_toxicity_design_space,yes_supporting_chemistry_design_module,"Added in v1.0 as a supporting backbone-chemistry module because it expands the design space around PS replacement/reduction, charge-neutral phosphorus linkages, conjugation, uptake, and activity.",source_metadata,no,CC BY 4.0
LI_FXR_JNK_G0S2_TRIPTOLIDE_HEPATOTOXICITY_2025,FXR as a pivotal role linking JNK and G0s2 mitigates triptolide-induced hepatotoxicity through the regulation of metabolic disorder of liver,2025,drug_induced_liver_injury_metabolic_pathway_siRNA_mechanism_primary,10.1016/j.phrs.2025.107738,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,triptolide_DILI_ALT_AST_JNK_FXR_G0s2_bile_acids_lipids_carnitine_siRNA_in_vitro_metabolic_hepatotoxicity_context,DILI|triptolide|ALT|AST|JNK|FXR|G0s2|siRNA|bile_acid|fatty_acid|carnitine|metabolic_disorder|oxidative_stress,supporting_liver_injury_pathway_module_not_oligo_specific_but_useful_for_liver_toxicity_mechanistic_covariates,yes_supporting_liver_injury_pathway_module,"Added in v1.0 as supporting hepatotoxicity biology because it provides ALT/AST, metabolic-disorder, FXR/JNK/G0s2, and siRNA knockdown context that can support liver-toxicity mechanism features.",source_metadata,no,CC BY 4.0
JEON_COP1_HCC_LIPID_STEMNESS_SIRNA_2026,Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness,2026,HCC_siRNA_lipid_metabolism_context,10.1111/gtc.70108,CC BY 4.0; context only unless later promoted,COP1_siRNA_HCC_lipid_metabolism_stemness_AKR1D1_TMEM65_context,siRNA|COP1|HCC|lipid_metabolism|stemness|AKR1D1|TMEM65|ROS,context_HCC_lipid_metabolism_siRNA_but_not_therapeutic_oligo_toxicity_or_delivery_safety,triage_deferred_context_only,"Deferred from v1.0 module integration because it is HCC biology and siRNA functional validation rather than therapeutic oligo toxicity, delivery, ADME, or liver-enzyme safety.",source_metadata,no,CC BY 4.0
SCHLEGEL_GKAC539_DUPLICATE_UPLOAD_2022,Duplicate upload of From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,2022,duplicate_upload_not_integrated_separately,10.1093/nar/gkac539,duplicate of source SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,duplicate_upload_skipped,duplicate_ESCplus_GalNAc_siRNA_seed_pairing_safety,duplicate_of_direct_high_value_source,triage_duplicate_not_added_as_separate_module,"The gkac539 PDF is the same article as the uploaded From bench to bedside PDF, so it is represented once to avoid double-counting evidence.",source_metadata,no,CC BY 4.0
BUREL_GAPMER_RNASEH1_LONG_PREMRNA_HEPATOTOX_2016,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts,2016,direct_ASO_gapmer_hepatotoxicity_mechanism_primary_transcriptomics,10.1093/nar/gkv1210,CC BY 4.0; generated variables only; no source figures/tables/sequences reproduced,high_affinity_gapmer_LNA_cEt_RNaseH1_promiscuous_offtarget_very_long_pre_mRNA_ALT_AST_hepatotoxicity_mechanism,ASO|gapmer|LNA|cEt|MOE|RNase_H1|off_target|very_long_pre_mRNA|ALT|AST|transaminitis|transcriptomics,direct_high_value_ASO_hepatotoxicity_mechanism_module,yes_direct_high_value_module,"Added in v1.0 because it is a core mechanistic ASO hepatotoxicity paper connecting high-affinity gapmer chemistry, RNase H1 dependence, transcriptomic off-target reduction, very long pre-mRNAs, and ALT/AST liver injury.",source_metadata,no,CC BY 4.0
JIANG_AOC_FREE_ASO_PAYLOAD_HYBRIDIZATION_LCMS_2024,Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS,2024,ASO_bioanalysis_PK_PD_measurement_primary_method,10.1080/17576180.2024.2368339,CC BY-NC-ND 4.0; generated variables only; no source figures/tables/text reproduced,free_ASO_payload_AOC_Fab_ASO_hybridization_LCMS_tissue_PK_biodistribution_parent_linker_interference_methodology,ASO|antibody_oligonucleotide_conjugate|Fab_ASO|hybridization_LC-MS/MS|free_payload|PK|PD|biodistribution|tissue_matrix|linker_interference,measurement_quality_reproducibility_PK_biodistribution_module_for_ASO_payload_quantification,yes_supporting_measurement_quality_module,"Added in v1.0 as a rigor/reproducibility module because Phase 2 reviewers may care how oligo exposure, tissue distribution, payload release, and parent/linker/metabolite specificity can be quantified.",source_metadata,no,CC BY 4.0
WAN_PUM1_EXOSOMES_MASLD_HSC_FIBROSIS_2025,Hepatocyte-derived Pumilio1-enriched exosomes inhibit HSC activation by suppressing tropomyosin-4 translation,2025,MASLD_liver_fibrosis_exosome_RNA_binding_shRNA_siRNA_primary,10.1097/HC9.0000000000000759,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,PUM1_hepatocyte_exosome_MASLD_lipotoxic_death_HSC_activation_TPM4_translation_AAV8_shRNA_siRNA_context,siRNA|shRNA|AAV8|PUM1|exosome|MASLD|HSC_activation|fibrosis|TPM4|lipotoxicity|hepatocyte_stress,supporting_liver_fibrosis_lipotoxicity_and_RNA_tool_context_not_direct_therapeutic_oligo_toxicity,yes_supporting_liver_fibrosis_context_module,"Added in v1.0 as supporting liver-biology context because it provides MASLD/fibrosis, hepatocyte-HSC crosstalk, PUM1 perturbation with shRNA/siRNA tools, and exosome-mediated hepatic injury/fibrosis context.",source_metadata,no,CC BY 4.0
ZHU_HMMR_HCC_4MU_SIRNA_2026,HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models,2026,HCC_target_validation_siRNA_context,10.14670/HH-18-937,CC BY 4.0; context only unless later promoted,HMMR_siRNA_HCC_drug_resistant_cell_proliferation_migration_4MU_context,siRNA|HMMR|HCC|4-MU|drug_resistance|xenograft|migration|proliferation,context_HCC_target_validation_but_not_therapeutic_oligo_toxicity_or_delivery_safety,triage_deferred_context_only,"Deferred in v1.0 because it is useful HCC biology and siRNA target validation, but lower immediate value for OligoTox hepatotoxicity prediction than direct ASO toxicity and bioanalysis sources.",source_metadata,no,CC BY 4.0
GHOLIKHANI_APTAMER_BREAST_CANCER_REVIEW_2022,"Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics",2022,aptamer_review_context_only,10.3390/ijms232214475,CC BY 4.0; review context only unless later promoted,aptamer_delivery_diagnostics_therapeutics_review_context,aptamer|SELEX|drug_delivery|diagnostics|breast_cancer|nanoparticle_conjugate,low_direct_value_for_OligoTox_liver_toxicity_prediction,triage_deferred_review_context_only,"Deferred in v1.0 because it is a review focused on breast cancer aptamers rather than oligo-induced hepatotoxicity, liver delivery, or therapeutic oligo safety readouts.",source_metadata,no,CC BY 4.0
JOSHI_BEPIROVIRSEN_B_TOGETHER_IMMUNOMODULATION_2026,Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study),2026,clinical_biomarker_original_article,10.1007/s12072-025-10917-0,open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_ASO_clinical_ALT_immunomodulation_module,unconjugated_ASO|HBV|ALT|HBsAg|immune_biomarkers|transcriptomics|proteomics,direct_clinical_ASO_ALT_and_hepatocyte_killing_context,yes_direct_module,"Adds clinical ASO biomarker layer for interpreting ALT increases, infected-hepatocyte killing, HBsAg decline, immune activation, and transcript/protein timing.",source_metadata,no,CC BY 4.0
TSUBOI_SNA_ASO_SGLT2_KIDNEY_SYSTEMIC_SAFETY_2025,In vivo efficacy and safety of systemically administered serinol nucleic acid-modified antisense oligonucleotides in mouse kidney,2025,preclinical_original_article,10.1016/j.omtn.2024.102387,open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_ASO_chemistry_delivery_safety_module,SNA-ASO|gapmer|PS|MOE comparator|SGLT2|kidney uptake|liver safety,supporting_systemic_ASO_safety_and_liver_damage_comparator_context,yes_supporting_module,"Adds serinol nucleic acid ASO chemistry, systemic delivery, kidney uptake, duration, glucosuria PD, and liver-safety comparison against MOE-ASO context.",source_metadata,no,CC BY 4.0
KANNAN_POLYAMINE_PLNP_RNA_DELIVERY_SAFETY_2025,Incorporation of a polyamine into lipid nanoparticles increases the endosomal release and transfection of nucleic acids without toxicity,2025,delivery_platform_original_article,10.1016/j.jconrel.2025.114366,CC BY-NC open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_LNP_RNA_delivery_safety_module,LNP|polyamine|mRNA|siRNA|endosomal_escape|factor_VII|liver_delivery|toxicity,supporting_RNA_delivery_safety_and_liver_transfection_context,yes_supporting_module,"Adds p-LNP endosomal escape, liver expression, siRNA ED50 improvement, RNA stability, pH buffering, and no significant liver toxicity context.",source_metadata,no,CC BY 4.0
TAKENOYA_GALP_HFD_LIVER_TRANSCRIPTOME_METABOLOME_2023,Transcriptomic and metabolome analyses of liver in high-fat diet mice after intranasal GALP,2023,liver_omics_original_article,10.3390/ijms242115825,CC BY open-access article; deferred from core generation,deferred_liver_metabolism_context,peptide|GALP|HFD|liver transcriptome|metabolome|bile acids|fatty acid metabolism,deferred_not_oligo_specific_liver_metabolism_context,triage_deferred_context_only,"Useful liver metabolism/omics background, but peptide/obesity focused and not sufficiently oligonucleotide-toxicity-specific for a new core module.",source_metadata,no,CC BY 4.0
SHEVELEV_SIRNA_THERAPEUTICS_REVIEW_2025,siRNA therapeutics for the treatment of hereditary diseases and other conditions: A review,2025,review,10.3390/ijms26178651,CC BY open-access review; deferred from core generation,deferred_review_context,siRNA|LNP|GalNAc|approved therapeutics|clinical trials,deferred_review_only_background,triage_deferred_review_only,"Broad review useful for narrative/background, but not used as a primary data-generating module to avoid review-only signal inflation.",source_metadata,no,CC BY 4.0
VAN_LEEUWEN_ASO_MULTIOMICS_TIME_RESOLVED_SAFETY_2026,Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach,2026,ASO_multiomics_original_article,10.1093/narmme/ugag016,CC BY-NC open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_ASO_safety_transcriptomics_proteomics_module,RNase_H1_ASO|LNA_gapmer|off-target|RNAseq|proteomics|ALT|HepG2|time_course,direct_ASO_liver_toxicity_and_off_target_safety_assessment,yes_direct_module,"Adds time-resolved ASO safety assessment with RNA/protein off-target comparison, toxic vs non-toxic ASO separation, HepG2 and mouse ALT context, and proteomics as complement to RNAseq.",source_metadata,no,CC BY 4.0
RIDER_SLN360_LPA_GALNAC_SIRNA_PRECLINICAL_TOX_2022,"Preclinical Toxicological Assessment of A Novel siRNA, SLN360, Targeting Elevated Lipoprotein(a) in Cardiovascular Disease",2022,preclinical_toxicology_original_article,10.1093/toxsci/kfac067,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_GalNAc_siRNA_preclinical_safety_module,GalNAc-siRNA|LPA|Lp(a)|rat|NHP|PK|TK|off-target|ALT|ALP|cytokine|complement,direct_preclinical_GalNAc_siRNA_liver_kidney_safety_and_toxicology_context,yes_direct_module,"Adds liver-targeted GalNAc-siRNA toxicology, in silico off-target screening, primary human hepatocyte specificity, rat/NHP 29-day safety, tissue distribution, reversibility, cytokine/complement/genotoxicity checks, and platform-effect labeling.",source_metadata,no,CC BY 4.0
MA_KUPFFER_BIOMIMETIC_ZIF8_BRCC3_SIRNA_SRLI_2025,Kupffer cells biomimetic nanoparticles alleviate sepsis related liver injury,2025,nanomedicine_siRNA_original_article,10.1186/s12951-025-03860-7,CC BY-NC-ND open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_siRNA_liver_injury_nanoparticle_delivery_module,siRNA|BRCC3|Kupffer_cell|ZIF-8|extracellular_vesicle|NLRP1|sepsis_liver_injury|LPS|CLP,supporting_liver_injury_inflammation_and_targeted_siRNA_delivery_context,yes_supporting_module,"Adds Kupffer-cell biomimetic nanoparticle delivery, BRCC3 siRNA, NLRP1 inflammasome biology, LPS/CLP sepsis-related liver injury context, and liver-enrichment/targeted uptake variables.",source_metadata,no,CC BY 4.0
LI_PKHD1_ARPKD_ASO_SPLICE_RESCUE_2023,A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease,2023,ASO_splicing_original_article_deferred,10.3390/jcm12041428,CC BY open-access article; deferred from core generation,deferred_ASO_splicing_rare_disease_context,ASO|splice_switching|PKHD1|ARPKD|pseudoexon|kidney|hepatic_fibrosis,deferred_low_direct_oligotox_hepatotoxicity_signal,triage_deferred_context_only,"Potentially useful ASO splice-correction context, but deferred because it has limited direct oligo toxicity, liver enzyme, or hepatotoxicity prediction signal.",source_metadata,no,CC BY 4.0
JIA_ATP7B_WILSON_MICROARRAY_DIAGNOSTIC_2022,Laboratory and clinical evaluation of a microarray for the detection of ATP7B mutations in Wilson disease in China,2022,diagnostic_microarray_original_article_deferred,10.1002/jcla.24735,CC BY-NC-ND open-access article; deferred from core generation,deferred_liver_genetic_diagnostics_context,oligonucleotide_microarray|ATP7B|Wilson_disease|diagnostics|mutation_detection,deferred_diagnostic_liver_disease_context_not_therapeutic_oligo_toxicity,triage_deferred_context_only,"Useful liver-disease genetic diagnostics context, but not a therapeutic oligo toxicity source and therefore not used for new core rows.",source_metadata,no,CC BY 4.0
BAI_EZH2_EXON_SKIPPING_HCC_ASO_2025,Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma,2025,splice_switching_ASO_liver_cancer_original_article,10.1016/j.ymthe.2025.02.032,publisher article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_liver_ASO_splice_switching_efficacy_module,MOE_PS_ASO|splice_switching|exon_skipping|EZH2|HCC|xenograft|liver_accumulation|H3K27me3,supporting_liver_ASO_therapeutic_context_and_splice_switching_design_features,yes_supporting_module,"Adds liver/HCC splice-switching ASO design, exon-skipping optimization, peripheral tissue/liver uptake context, tumor efficacy, and non-RNase-H steric-blocking ASO mechanism variables.",source_metadata,no,CC BY 4.0
KABURAGI_TOC_HDO_DRG_SCIATIC_SYSTEMIC_DELIVERY_2022,Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve,2022,HDO_ASO_delivery_original_article,10.1016/j.omtn.2022.05.006,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_extrahepatic_ASO_HDO_delivery_module,DNA_RNA_HDO|gapmer_ASO|alpha_tocopherol|DRG|sciatic_nerve|systemic_delivery|RNase_H1,supporting_extrahepatic_delivery_and_biodistribution_context_for_oligo_safety_modeling,yes_supporting_module,"Adds DNA/RNA heteroduplex oligonucleotide delivery variables, ligand-conjugated complementary RNA, systemic distribution beyond liver, dose/frequency context, and target knockdown in DRG/sciatic nerve.",source_metadata,no,CC BY 4.0
DAI_XIST_MIR663A_GPX4_HSC_FERROPTOSIS_FIBROSIS_2026,Long noncoding RNA X-inactive-specific transcript promotes hepatic fibrosis by suppressing ferroptosis in hepatic stellate cells via the miR-663a/GPX4 axis,2026,lncRNA_siRNA_shRNA_liver_fibrosis_original_article,10.3389/fphys.2025.1734886,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_RNA_perturbation_HSC_ferroptosis_fibrosis_module,lncRNA|siRNA|shRNA|XIST|miR-663a|GPX4|HSC|ferroptosis|ALT|AST|HYP|hepatic_fibrosis,supporting_liver_fibrosis_HSC_activation_ferroptosis_and_RNA_perturbation_context,yes_supporting_module,"Adds HSC activation, XIST knockdown, miR-663a/GPX4 ferroptosis axis, ALT/AST/HYP liver injury markers, and fibrosis rescue/antagonist logic.",source_metadata,no,CC BY 4.0
YUAN_LIVTAC_GALNAC_PROTAC_BRD4_FIBROSIS_2025,Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models,2025,liver_targeted_GalNAc_PROTAC_original_article_deferred,10.7150/thno.113852,CC BY open-access article; deferred from core oligo generation,deferred_GalNAc_non_oligo_liver_targeting_context,GalNAc|ASGPR|PROTAC|BRD4|HSC|fibrosis|CCl4|CDAA-HFD|transcriptomics|metabolomics,deferred_useful_liver_targeting_and_fibrosis_context_but_not_oligonucleotide_therapeutic,triage_deferred_context_only,"Useful liver-targeting comparator and fibrosis biology source, but deferred because the active therapeutic is a GalNAc-PROTAC rather than an oligonucleotide.",source_metadata,no,CC BY 4.0
CAI_LYCIUM_POLYSACCHARIDES_ETHANOL_LIVER_INJURY_2025,Lycium barbarum Polysaccharides Alleviate Ethanol-Induced Liver Injury by Activating PPAR-alpha and Inhibiting NLRP-3/Caspase-1-Mediated Pyroptosis,2025,hepatoprotection_original_article_deferred,10.1002/fsn3.70172,CC BY open-access article; deferred from core generation,deferred_non_oligo_hepatoprotection_context,ethanol_liver_injury|PPAR-alpha|NLRP3|caspase-1|pyroptosis|siRNA_control,deferred_liver_injury_pathway_context_but_non_oligo_nutraceutical_intervention,triage_deferred_context_only,"Contains useful ALT/AST/TG and PPAR-alpha siRNA pathway context, but deferred because the therapeutic intervention is polysaccharide/nutraceutical rather than oligo-centric.",source_metadata,no,CC BY 4.0
LIN_GALNAC_SICIDEB_MASH_STEATOSIS_FIBROSIS_2025,Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models,2025,GalNAc_siRNA_MASH_original_article,10.1016/j.omtn.2025.102567,CC BY-NC-ND open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_liver_GalNAc_siRNA_MASH_safety_efficacy_module,GalNAc-siRNA|CIDEB|MASH|MASLD|ASGPR|2prime-OMe|2prime-F|5prime-VP|isoGNA|off-target|steatosis|fibrosis|liver_toxicity,direct_liver_targeted_siRNA_safety_offtarget_and_MASH_fibrosis_readout_context,yes_direct_module,"Adds direct GalNAc-siRNA hepatocyte-targeted CIDEB silencing, isoGNA specificity/off-target mitigation, AAV8-hCIDEB in vivo evaluation, MASH steatosis/fibrosis endpoints, and no-observed-toxicity context.",source_metadata,no,CC BY 4.0
KURODA_ASO_LATE_ONSET_NEUROTOX_5CP_MODIFICATIONS_2025,Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications,2025,ASO_CNS_toxicity_chemical_modification_original_article,10.1016/j.omtn.2025.102692,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_ASO_toxicity_mitigation_chemistry_module,gapmer_ASO|PS|LNA|MOE|2prime-OMe|5prime-cyclopropylene|late-onset_neurotoxicity|p53|paraspeckle|p54nrb|chemical_mitigation,supporting_cross-organ_ASO_toxicity_mechanism_and_chemistry_mitigation_context,yes_supporting_module,Adds ASO toxicity structure-activity and structure-toxicity logic: site-specific gap modifications can mitigate late-onset neurotoxicity while preserving knockdown activity; useful for general oligo safety modeling beyond liver.,source_metadata,no,CC BY 4.0
KHORSANDI_GALNAC_SICEBPB_MASLD_HOMEOSTASIS_2026,GalNAc-conjugated siRNA targeting C/EBPbeta reverses metabolic dysfunction and restores liver homeostasis in a murine MASLD model,2026,GalNAc_siRNA_MASLD_original_article,10.1016/j.omtn.2026.102865,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,direct_liver_GalNAc_siRNA_MASLD_safety_homeostasis_module,GalNAc-siRNA|C/EBPbeta|MASLD|steatosis|liver_function|albumin|bilirubin|ALT|AST|hepatocyte_delivery,direct_liver_GalNAc_siRNA_safety_and_functional_liver_homeostasis_context,yes_direct_module,"Adds hepatocyte-specific GalNAc-siRNA target engagement, metabolic and liver-function readouts, steatosis reduction, unchanged ALT/AST safety context, and continued high-fat-diet stress context.",source_metadata,no,CC BY 4.0
WANG_TRIVALENT_DISULFIDE_MASKED_ODN_DELIVERY_2024,Trivalent Disulfide Unit-Masked System Efficiently Delivers Large Oligonucleotide,2024,oligonucleotide_delivery_chemistry_original_article,10.3390/molecules29174223,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,supporting_oligonucleotide_delivery_chemistry_module,SS-ODN|trivalent_disulfide_unit|thiol_exchange|cellular_uptake|liver_distribution|endocytosis_independent|low_cytotoxicity,supporting_delivery_chemistry_and_liver_distribution_context_for_large_oligonucleotides,yes_supporting_module,"Adds non-liposomal trivalent disulfide-unit delivery chemistry, cellular uptake, thiol-blocking dependence, low cytotoxicity, and rapid liver distribution context.",source_metadata,no,CC BY 4.0
NASTASE_NSCLC_LONG_TERM_SURVIVAL_MARKERS_2022,Molecular Markers for Long-term Survival in Stage IIIA (N2) NSCLC Patients,2022,cancer_genomics_microarray_WES_article_deferred,10.21873/cgp.20306,freely accessible article; deferred from oligo toxicity generator,deferred_non_oligo_NSCLC_genomics_context,NSCLC|microarray|WES|survival|SWI/SNF|VISTA|chemotherapy_response,deferred_not_oligonucleotide_not_liver_toxicity_specific,triage_deferred_context_only,"Deferred because it is a lung-cancer survival-marker study without therapeutic oligonucleotide toxicity, liver-safety, delivery, or oligo chemistry relevance.",source_metadata,no,CC BY 4.0
ZHANG_MPTP_OXMTDNA_MASH_ITPR3_NLRP3_2025,MPTP mediated Ox-mtDNA release inducing macrophage pyroptosis and exacerbating MCD-induced MASH via ITPR3/Ca2+/NLRP3 pathway,2025,primary_research_open_access,10.1186/s12967-025-07302-8,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce/adapt source figures/tables/text,supporting_liver_injury_pyroptosis_mechanism,siRNA|AAV|MASH|macrophage_pyroptosis|NLRP3,supporting_liver_injury_mechanism,yes_supporting_module,"Adds Ox-mtDNA, mPTP, ITPR3/Ca2+/NLRP3, macrophage pyroptosis, ALT/AST, MASH progression, siRNA/AAV perturbation context.",source_metadata,no,CC BY 4.0
YANG_NG2_CSPG4_SIRNA_LIVER_FIBROSIS_2023,Neuron-Glial Antigen 2 participates in liver fibrosis via regulating BMSC differentiation to myofibroblast,2023,primary_research_open_access,10.3390/ijms24021177,CC BY 4.0; use as evidence/context only; do not reproduce source figures/tables/text,direct_siRNA_liver_fibrosis_module,siRNA|Cspg4|NG2|liver_fibrosis|ALT_AST,direct_liver_injury_fibrosis_readouts,yes_direct_module,"Adds Cspg4/NG2 siRNA, fibrotic liver models, myofibroblast differentiation, collagen, ALT/AST, steatosis and inflammation improvement context.",source_metadata,no,CC BY 4.0
HUAYAMARES_HNSCC_LNP_TUMOR_TROPISM_LIVER_DETARGET_2023,High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo,2023,primary_research_manuscript,10.1016/j.jconrel.2023.04.005,publisher manuscript; use as evidence/context only; do not reproduce source figures/tables/text,supporting_LNP_biodistribution_liver_detargeting_module,LNP|mRNA_delivery|tumor_tropism|liver_offtarget_delivery,supporting_delivery_biodistribution_and_liver_offtarget_context,yes_supporting_module,"Adds high-throughput in vivo LNP screening, DNA barcode readout, HNSCC delivery, and minimized off-target liver hepatocyte delivery context.",source_metadata,no,CC BY 4.0
HUANG_NANOPARTICLE_SIRNA_ONCOLOGY_REVIEW_2022,Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic siRNA in Precision Oncology,2022,review_open_access,10.3390/pharmaceutics14081586,"CC BY 4.0; review-only; use for narrative/context, not core generated table",deferred_review_context,siRNA|nanoparticles|oncology_delivery,deferred_review_only,triage_deferred_review_only,Review source useful for background but not added as a source-specific generation module to avoid review-only noise.,source_metadata,no,CC BY 4.0
RUCHI_EVOLUTION_ASO_CHEMISTRY_DELIVERY_REVIEW_2025,Evolution of Antisense Oligonucleotides: Navigating Nucleic Acid Chemistry and Delivery Challenges,2025,review_author_manuscript,10.1080/17460441.2024.2440095,"author manuscript/review; use for narrative/context, not core generated table",deferred_review_context,ASO|chemistry|delivery|clinical_development,deferred_review_only,triage_deferred_review_only,Review source useful for final narrative/license/background but not added as a source-specific generated table.,source_metadata,no,CC BY 4.0
SINHA_NNMT_ASO_MACROPHAGE_ATHEROSCLEROSIS_2025,NAD metabolism regulates proliferation of macrophages in atherosclerosis,2025,ASO_siRNA_immunometabolism_original_article,10.1161/ATVBAHA.125.323185,author manuscript/open access via PMC; use as evidence/context only,supporting_systemic_ASO_macrophage_immunometabolism_module,ASO|siRNA|NNMT|NAD|macrophage_proliferation|macrophage_apoptosis,supporting cross-organ ASO/siRNA pharmacology; not direct hepatotoxicity,yes_supporting_module,Adds systemic ASO versus selective siRNA contrast and macrophage immunometabolism context.,source_metadata,no,CC BY 4.0
YAMAGUCHI_TY1_ORAL_NCRNA_MACROPHAGE_C2_2025,"Oral Bioavailability of a Noncoding RNA Drug, TY1, That Acts on Macrophages",2025,oral_ncRNA_delivery_original_article,10.1002/jex2.70081,CC BY open-access article; use as evidence/context only,supporting_oral_macrophage_active_ncRNA_delivery_safety_module,synthetic_ncRNA|LNP|casein_chitosan_C2_micelles|oral_delivery|macrophages|monocytes|tolerability|liver_enzymes,supporting RNA delivery/tolerability context; not direct hepatotoxicity,yes_supporting_module,"Adds oral RNA delivery, C2 micelle protection, macrophage/monocyte exposure, and tolerability/liver-enzyme context.",source_metadata,no,CC BY 4.0
YU_DUAL_RGD_DSRBD_18HIS_TUMOR_SIRNA_DELIVERY_2021,Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery,2021,siRNA_delivery_nanocarrier_original_article,10.3390/pharmaceutics13122182,CC BY open-access article; use as evidence/context only,supporting_extrahepatic_tumor_targeted_siRNA_delivery_safety_module,siRNA|RGD|dsRBD|18His|integrin_avb3|endosomal_escape|tumor_delivery|low_toxicity,supporting delivery and biodistribution context beyond liver,yes_supporting_module,"Adds non-cationic siRNA carrier, RNase protection, endosomal escape, tumor targeting, and low-toxicity delivery context.",source_metadata,no,CC BY 4.0
LARIJANI_P21_SHRNA_CARTILAGE_REPAIR_2026,p21 Knockdown as a Therapeutic Strategy for Focal Cartilage Injury Repair,2026,lentiviral_shRNA_cartilage_original_article_deferred,10.1096/fj.202600387RRR,CC BY open-access article; deferred,deferred_lentiviral_shRNA_cartilage_context,lentiviral_shRNA|p21|cartilage|hepatic_offtarget_transduction,deferred: not therapeutic oligo liver-toxicity source,triage_deferred_context_only,"Deferred because it is lentiviral shRNA cartilage repair, not an oligo hepatotoxicity dataset source.",source_metadata,no,CC BY 4.0
THONGSRI_PANDURATIN_A_HBV_HNF1A_2026,Panduratin A suppresses hepatitis B virus by targeting HNF1alpha,2026,small_molecule_HBV_liver_model_article_deferred,10.1186/s13020-025-01285-w,CC BY open-access article; deferred,deferred_non_oligo_HBV_small_molecule_liver_context,panduratin_A|HBV|HNF1alpha|siRNA_mechanistic_knockdown|3D_liver_spheroid,"deferred: small-molecule antiviral, not oligo toxicity",triage_deferred_context_only,"Deferred because siRNA is mechanistic, not the therapeutic modality.",source_metadata,no,CC BY 4.0
RING_PIKFYVE_APILIMOD_HEV_ENTRY_2026,Phosphoinositide kinase PIKfyve inhibitor apilimod blocks hepatitis E virus infection,2026,host_directed_HEV_antiviral_original_article_deferred,10.1136/egastro-2025-100348,CC BY-NC; no commercial reuse; deferred context-only source,deferred_non_oligo_host_directed_hepatocyte_antiviral_context,apilimod|PIKfyve|HEV_entry|siRNA_knockdown_mechanistic_validation,liver/hepatocyte model context but not therapeutic oligo toxicity,triage_deferred_context_only,Deferred because the intervention is a small-molecule PIKfyve inhibitor; siRNA is used to validate mechanism rather than as therapeutic oligo modality.,source_metadata,no,CC BY 4.0
SADDIQUE_RNAI_CARDIAC_FAILURE_SYSTEMATIC_REVIEW_2024,Safety and effectiveness of interference RNA based therapeutics in cardiac failure: A systematic review,2024,RNAi_cardiac_failure_systematic_review_deferred,10.1016/j.hrtlng.2024.08.015,CC BY 4.0; review-only deferred context source,deferred_review_only_cardiac_RNAi_context,RNAi|patisiran|revusiran|cardiac_failure|adverse_effects,review-only and cardiac-focused; not direct OligoTox hepatotoxicity source,triage_deferred_context_only,Deferred because review-only sources are reserved for narrative/background rather than row-level generation.,source_metadata,no,CC BY 4.0
RAMESH_KUMAR_RPSAP52_LNA_GAPMER_OVARIAN_PDOX_2025,Specific targeting of the pseudogene RPSAP52 reduces ovarian tumor growth in patient-derived orthoxenograft models,2025,LNA_GapmeR_lncRNA_pseudogene_original_article,10.1016/j.ejca.2025.116040,CC BY-NC; source used as scientific context/provenance only,supporting_gapmer_ASO_extrahepatic_oncology_safety_module,LNA_GapmeR|pseudogene|RPSAP52|HMGA2|ovarian_cancer|PDOX|toxicity_context,supporting ASO/GapmeR modality and tolerability context outside liver; not direct hepatotoxicity,yes_supporting_module,Adds antisense LNA GapmeR targeting of a noncoding pseudogene in ovarian cancer preclinical models without evident toxicity.,source_metadata,no,CC BY 4.0
KOSTYUSHEVA_BIOLOGICS_HYB_TARGETED_RNA_DELIVERY_2025,Biologics-based technologies for highly efficient and targeted RNA delivery,2025,biologics_based_RNA_delivery_original_article,10.1016/j.ymthe.2024.11.004,Elsevier/Molecular Therapy article; source used as scientific context/provenance only; do not redistribute source figures/tables/text,supporting_EMNV_liposome_hybrid_siRNA_delivery_module,EMNV|hybrid_EMNV_liposome|siRNA|PTGFRN|CD63|liver_targeting|RNA_loading|endosomal_escape,"supporting delivery, liver-targeting, RNA loading and safety/biocompatibility context",yes_supporting_module,"Adds biological nanoparticle/hybrid nanovesicle RNA loading, targeting, intracellular delivery, and liver-targeted siRNA delivery context.",source_metadata,no,CC BY 4.0
BHATIA_PELACARSEN_LPA_ASO_REVIEW_2025,Pelacarsen: Mechanism of action and Lp(a)-lowering effect,2025,clinical_ASO_review_deferred,10.1016/j.jacl.2025.06.004,CC BY-NC-ND; review-only deferred context source,deferred_review_only_pelacarsen_clinical_ASO_context,pelacarsen|GalNAc_ASO|LPA|apo(a)|Lp(a)|ASCVD|clinical_safety,useful clinical ASO background but review-only; not row-level source,triage_deferred_context_only,Deferred from generated source tables because it is a review; useful later for final narrative and clinical context.,source_metadata,no,CC BY 4.0
BARON_ALPHA_GAG_MS2_CRISPR_RNA_DELIVERY_2022,Improved alpharetrovirus-based Gag.MS2 particles for efficient and transient delivery of CRISPR-Cas9 into target cells,2022,CRISPR_RNA_delivery_original_article_deferred,10.1016/j.omtn.2021.12.033,CC BY; deferred source used as context only,deferred_gene_editing_vector_delivery_context_only,Gag.MS2|Cas9_mRNA|sgRNA|primary_hepatocytes,primary hepatocyte delivery context but not therapeutic oligo toxicity data,triage_deferred_context_only,"Deferred because the core intervention is transient CRISPR-Cas9 delivery, not oligo toxicology.",source_metadata,no,CC BY 4.0
MADILL_HALLORAN_MMDX_TRANSPLANT_DIAGNOSTICS_2024,Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope Diagnostic System,2024,transplant_molecular_diagnostics_review_deferred,10.1042/CS20220530,CC BY; deferred source used as context only,deferred_diagnostics_and_machine_learning_context_only,microarray|gene_expression|machine_learning|transplant_rejection,general diagnostics rigor context but not oligo therapeutic toxicity data,triage_deferred_context_only,"Deferred because it is diagnostics/machine-learning background, not oligo toxicity or delivery.",source_metadata,no,CC BY 4.0
STEEL_CD81_GALNAC_SIRNA_MALARIA_PROTECTION_2025,Protection from malaria infection using liver-targeted siRNA,2025,GalNAc_siRNA_liver_prophylaxis_original_article,10.1016/j.omtm.2025.101516,CC BY; generated variables only; do not reproduce source figures/tables/text,direct_liver_targeted_GalNAc_siRNA_hepatocyte_knockdown_module,GalNAc-siRNA|CD81|hepatocyte|ASGPR|malaria_prevention|humanized_liver_mouse,"direct liver-targeted siRNA module with hepatocyte receptor silencing, durability, dose response, and infection-protection endpoints",yes_direct_module,Adds direct GalNAc-siRNA hepatocyte-targeting and host-factor protection context.,source_metadata,no,CC BY 4.0
LI_RBM39_HEPATOCYTE_IFN_INNATE_IMMUNITY_2025,RBM39 shapes innate immunity by controlling the expression of key factors of the interferon response,2025,hepatocyte_innate_immunity_original_article,10.3389/fimmu.2025.1568056,CC BY; generated variables only; do not reproduce source figures/tables/text,supporting_hepatocyte_interferon_and_oligo_immune_activation_module,RBM39|siRNA_knockdown|TLR3|RIG-I|MDA5|IRF3|STAT1|STAT2|IFN|poly(I:C),supporting dsRNA/TLR3/RIG-I/MDA5/interferon-response context for oligo immune-activation modeling,yes_supporting_module,Adds hepatocyte innate immune-response context relevant to oligo safety modeling.,source_metadata,no,CC BY 4.0
DMITRIEV_GALNAC_SIRNA_PCSK9_LIQUID_PHASE_2026,Refined Design and Liquid-Phase Assembly of GalNAc-siRNA Conjugates: Comparative Efficiency Validation in PCSK9 Targeting,2026,GalNAc_siRNA_design_synthesis_original_article,10.3390/molecules31030476,CC BY; generated variables only; do not reproduce source figures/tables/text,direct_GalNAc_siRNA_design_synthesis_and_PCSK9_validation_module,GalNAc-siRNA|PCSK9|ASGPR|liquid-phase_conjugation|siRNA_design|Inclisiran_comparator,"design, synthesis, hepatocyte delivery, specificity, comparator, and PCSK9 validation context for GalNAc-siRNA model-readiness",yes_direct_module,"Adds GalNAc-siRNA sequence design, liquid-phase conjugation, comparator, and scalable synthesis context.",source_metadata,no,CC BY 4.0
KIM_LARP6_HSC_FIBROSIS_DSI_RNA_2026,RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis,2026,human_liver_fibrosis_dsiRNA_original_article,10.1172/JCI197923,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,direct_HSC_fibrosis_dsiRNA_and_human_MASH_MetALD_spheroid_module,Dicer substrate siRNA|LARP6|HSC|MASH|MetALD|collagen|3D liver spheroids,direct liver-fibrosis RNAi intervention and collagen/fibrogenic readout context in human MASH/MetALD models,yes_direct_module,"Adds HSC-specific LARP6 knockdown, collagen mRNA/translation regulation, fibrosis attenuation, and human liver spheroid context.",source_metadata,no,CC BY 4.0
SUBRAMANIAN_RNAI_RHEOSTAT_AAV_TRANSGENE_2023,RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes,2023,RNAi_transgene_control_original_article,10.1038/s41467-023-37774-5,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_GalNAc_siRNA_REVERSIR_AAV_expression_control_module,GalNAc-siRNA|shRNA|REVERSIR|AAV8|hepatocyte transgene expression|dose control,supports dose-control and reversibility concepts for liver-directed RNAi and gene-therapy safety engineering,yes_supporting_module,"Adds RNAi-based transgene rheostat, reversible silencing, and liver AAV expression control context.",source_metadata,no,CC BY 4.0
FRIEDRICH_AIGNER_THERAPEUTIC_SIRNA_REVIEW_2022,Therapeutic siRNA: State-of-the-Art and Future Perspectives,2022,siRNA_review_deferred,10.1007/s40259-022-00549-3,CC BY 4.0; deferred source used as context only,deferred_background_review_only,siRNA design|chemical modification|delivery|clinical landscape,background only; not used for row-level data generation,triage_deferred_context_only,Deferred because it is a review. Useful for final narrative but not row-level generated data.,source_metadata,no,CC BY 4.0
JANAS_GALNAC_SIRNA_OFFTARGET_RAT_HEPATOTOX_2018,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity,2018,GalNAc_siRNA_hepatotoxicity_mechanism_original_article,10.1038/s41467-018-02989-4,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,direct_seed_offtarget_rat_hepatotoxicity_module,GalNAc-siRNA|seed off-target|RISC loading|GNA modification|ALT|AST|rat hepatotoxicity,direct mechanistic evidence that seed-driven RNAi off-target effects can drive GalNAc-siRNA rat hepatotoxicity and can be mitigated by destabilizing seed pairing,yes_direct_module,"Adds dedicated mechanistic off-target hepatotoxicity and mitigation table, complementary to prior platform safety context.",source_metadata,no,CC BY 4.0
BERGEN_DILIMAP_TOXPREDICTOR_DILI_2025,A large-scale human toxicogenomics resource for drug-induced liver injury prediction,2025,DILI_toxicogenomics_original_article_supporting,10.1038/s41467-025-65690-3,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_human_hepatocyte_DILI_modeling_and_validation_module,primary human hepatocytes|RNA-seq|DILImap|ToxPredictor|DILI|machine learning|safety margins,"supports liver-toxicity modeling rigor, transcriptomic mechanism coverage, dose-resolved DILI prediction, and validation strategy",yes_supporting_module,"Adds toxicogenomics and ML validation context for DILI risk modeling, not oligo-specific but highly relevant to hepatotoxicity prediction rigor.",source_metadata,no,CC BY 4.0
GERETTI_RO7239958_GALNAC_LNA_ASO_HBV_PHASE1_2025,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",2025,clinical_GalNAc_LNA_ASO_phase1_original_article,10.1128/aac.00679-25,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,direct_clinical_LNA_ASO_PK_PD_safety_window_module,GalNAc-conjugated LNA ASO|PAPD5|PAPD7|HBV|HBsAg|transaminases|PK/PD,"direct clinical liver-targeted ASO safety, transaminase elevation, ASGPR saturation, narrow therapeutic-window context",yes_direct_module,"Adds clinical single-stranded LNA ASO PK/PD, ASGPR uptake saturation, PAPD5/7 knockdown predictions, and transaminase-safety boundary context.",source_metadata,no,CC BY 4.0
LIU_HYDROGEN_HNP_TGFB1_SIRNA_PULMONARY_FIBROSIS_2025,Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis,2025,inhaled_siRNA_delivery_original_article,10.1126/sciadv.adt2752,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_extrahepatic_nebulized_siRNA_delivery_and_macrophage_safety_module,nebulized siRNA|hybrid lipid nanoparticles|TGFb1 siRNA|pulmonary fibrosis|macrophage delivery|mucus barrier,supporting delivery/tolerability context outside liver; useful for modality breadth and macrophage immune-delivery modeling rather than direct liver toxicity,yes_supporting_module,"Adds aerosolized HNP/TGFb1 siRNA, mucus-barrier penetration, macrophage uptake, endosomal escape, and fibrosis-repair context.",source_metadata,no,CC BY 4.0
SUN_PCSK9_SIRNA_STING_CANCER_IMMUNOTHERAPY_2025,Silencing PCSK9 reshapes the spatiotemporal activation of STING for safe and effective cancer immunotherapy,2025,PCSK9_siRNA_STING_immunotherapy_original_article,10.1038/s41467-025-66630-x,standard/open access metadata; generated variables only; do not reproduce source figures/tables/text,supporting_siRNA_STING_hepatic_immune_toxicity_modulation_module,PCSK9 siRNA|STING agonist|innate immunity|liver toxicity mitigation|nanoparticle co-delivery,supports hepatic immune-toxicity mitigation logic and tissue-selective innate immune activation using siRNA co-therapy,yes_supporting_module,Adds PCSK9 siRNA as an immune-modulatory safety lever for STING agonist therapy and liver-vs-tumor toxicity boundary context.,source_metadata,no,CC BY 4.0
XIE_TOP2A_HCC_SCRNA_SIRNA_KNOCKDOWN_2025,Single cell-RNA sequencing reveal TOP2A as a key driver of hepatocellular carcinoma progression,2025,HCC_siRNA_knockdown_biology_deferred,10.1038/s41598-025-16785-w,open access; deferred source used as context only,deferred_HCC_target_validation_context_only,siRNA knockdown|TOP2A|HCC|scRNA-seq|HepG2|Huh7,"HCC target-validation biology; lower value for oligo-toxicity modeling than clinical ASO, delivery, or toxicity-mechanism sources",triage_deferred_context_only,"Deferred because siRNA is mainly a target-validation tool in HCC cells and does not add a strong toxicity, delivery, or safety module.",source_metadata,no,CC BY 4.0
WEISS_GYS1_ASO_POMPE_SKELETAL_MUSCLE_2025,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,2025,ASO_skeletal_muscle_original_article,10.1002/ctm2.70314,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_extrahepatic_ASO_tissue_safety_and_substrate_reduction_module,gapmer ASO|GYS1|Pompe disease|skeletal muscle|ERT combination|substrate reduction,supporting extrahepatic ASO specificity and tissue-effect context; useful for safety-boundary modeling and distinguishing liver vs muscle ASO effects,yes_supporting_module,"Adds systemic PS/cEt gapmer ASO targeting Gys1, skeletal-muscle glycogen reduction, ERT combination, and extrahepatic tissue-safety context.",source_metadata,no,CC BY 4.0
YU_SPTLC2_LNP_SIRNA_MASH_CERAMIDE_2025,Targeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH,2025,LNP_siRNA_MASH_original_article,10.1126/sciadv.adx2681,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/text,direct_hepatocyte_LNP_siRNA_MASH_ceramide_module,LNP-siRNA|SPTLC2|hepatocytes|MASH|ceramide|lipidomics|ALT_AST|fibrosis,"direct liver-targeted siRNA disease and safety context; links hepatocyte target knockdown to hepatic lipid injury, inflammation, steatosis, and MASH progression",yes_direct_module,"Adds LNP-mediated Sptlc2 siRNA, hepatocyte delivery, de novo ceramide pathway inhibition, MCD/CD-HFD MASH models, ALT/AST and fibrosis context.",source_metadata,no,CC BY 4.0
ZENG_PDL1_APTAMER_CD47_SIRNA_TREG_HCC_2025,Targeting tumor-infiltrating regulatory T cells: combining CD47 and PD-L1 inhibition via a novel aptamer-siRNA chimera,2025,aptamer_siRNA_chimera_HCC_immunotherapy_original_article,10.1186/s43556-025-00392-2,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_cell_selective_aptamer_siRNA_immune_oncology_module,aptamer-siRNA chimera|PD-L1 aptamer|CD47 siRNA|Treg|HCC|tumor microenvironment|immune checkpoint,supporting oligo delivery/selectivity and HCC immune microenvironment context; useful for modeling immune-targeted RNA therapeutics and off-tumor safety boundaries,yes_supporting_module,"Adds aptamer-siRNA selective binding/internalization, CD47 knockdown, PD-L1 targeting, Treg depletion, CD8 infiltration, and HCC antitumor context.",source_metadata,no,CC BY 4.0
WANG_THBS1_RILI_PROTEOMICS_SIRNA_2025,THBS1 as a candidate biomarker and fibrotic mediator in radiation-induced liver injury,2025,radiation_induced_liver_injury_proteomics_siRNA_original_article,10.3389/fphar.2025.1659870,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,supporting_liver_injury_biomarker_and_fibrosis_mechanism_module,siRNA knockdown|THBS1|RILI|TMT proteomics|JAK2_STAT3|COL5A|COL6A|plasma biomarker,supporting liver-injury/fibrosis biomarker and pathway context; siRNA used mechanistically to validate THBS1 effects on collagen/JAK2-STAT3 signaling,yes_supporting_module,"Adds radiation liver injury, THBS1 biomarker, proteomics, collagen deposition, and siRNA knockdown reversal of fibrotic signaling.",source_metadata,no,CC BY 4.0
LIU_NEDD4_NEFA_KETOTIC_COW_LIVER_2026,The E3 ubiquitin ligase NEDD4 protects against nonesterified fatty acid-induced hepatic inflammatory injury in ketotic cows,2026,bovine_ketosis_liver_injury_siRNA_mechanistic_deferred,10.3168/jds.2025-27574,CC BY 4.0; deferred source used as context only,deferred_non_therapeutic_siRNA_bovine_ketosis_context,siRNA knockdown|NEDD4|RIPK1|NEFA|ketotic cows|bovine hepatocytes|NF-kB,liver injury biology but bovine ketosis and mechanistic siRNA use only; low direct value for therapeutic oligo toxicity modeling,triage_deferred_context_only,Deferred because the study is dairy-cow ketosis biology and siRNA is a mechanistic perturbation tool rather than therapeutic oligo modality.,source_metadata,no,CC BY 4.0
CHEN_HNF4A_KETOTIC_COW_HEPATOCYTE_SIRNA_2025,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,bovine_ketosis_hepatocyte_siRNA_mechanistic_deferred,10.3168/jds.2025-26548,CC BY 4.0; deferred source used as context only,deferred_non_therapeutic_siRNA_bovine_ketosis_lipid_metabolism_context,siRNA knockdown|HNF4A|NEFA|FAO|CES1|CES2|ketotic cows|bovine hepatocytes,liver metabolic injury biology but bovine ketosis and mechanistic siRNA use only; low direct oligo-toxicity value,triage_deferred_context_only,Deferred because it is a bovine ketosis metabolism study; siRNA is target-validation rather than therapeutic oligo evidence.,source_metadata,no,CC BY 4.0
TATSUKAWA_TG_KERATIN_BILE_ACID_HEPATOCYTE_DEATH_2025,Transglutaminase-mediated cytokeratin modifications implicated in bile-acid-induced hepatocyte death,2025,cholestatic_liver_injury_original_article,10.1111/febs.70281,CC BY-NC; generated variables only; do not reproduce source figures/tables/text,supporting_bile_acid_hepatocyte_death_and_fibrosis_module,siRNA knockdown|TG1|TG2|K18|K8|GCDCA|hepatocyte apoptosis|cholestasis|fibrosis,"adds bile-acid-induced hepatocyte apoptosis, transglutaminase/cytokeratin aggregation, caspase activation, and siRNA-based rescue context",yes_supporting_module,Useful for modeling cholestatic liver-injury mechanisms and cytoskeletal stress/apoptosis readouts relevant to hepatotoxicity.,source_metadata,no,CC BY 4.0
ZHANG_TRIM16_YAP1_NRF2_SEPTIC_LIVER_INJURY_2026,TRIM16 mediates YAP1 K63-linked ubiquitination to alleviate sepsis-induced acute liver injury through YAP/Nrf2 axis in mice,2026,septic_liver_injury_original_article,10.1186/s13578-025-01517-4,CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,supporting_inflammation_oxidative_stress_liver_injury_module,siRNA knockdown|AAV9 overexpression|TRIM16|YAP1|Nrf2|ALT|AST|TNF-alpha|IL-6|oxidative stress,"adds acute inflammatory/oxidative-stress liver injury, ALT/AST dysfunction, siRNA worsening, and rescue-pathway context",yes_supporting_module,"Useful for modeling liver-injury safety boundaries, cytokine/ROS axes, and protective pathway modulation.",source_metadata,no,CC BY 4.0
ZHOU_TDEV_MEMBRANE_LEV_SIRNA_HCC_DELIVERY_2022,Tumour-derived extracellular vesicle membrane hybrid lipid nanovesicles enhance siRNA delivery by tumour-homing and intracellular freeway transportation,2022,advanced_siRNA_delivery_original_article,10.1002/jev2.12198,CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,supporting_EV_membrane_hybrid_siRNA_delivery_module,siRNA delivery|tumor-derived EV membrane|hybrid lipid nanovesicle|HCC|endosomal bypass|Golgi|ER|tumor homing,"adds advanced hepatocellular-carcinoma siRNA delivery, targeting, trafficking, and transfection-efficiency context",yes_supporting_module,"Useful for modeling delivery-system differences, intracellular trafficking, and tissue/cell targeting assumptions.",source_metadata,no,CC BY 4.0
KLEIN_NFI_CYP_HUMAN_LIVER_PHARMACOMETABOLISM_2025,Transcription factors of the Nuclear Factor I family control hepatocyte differentiation and cytochrome P450 activity in human liver,2025,human_liver_pharmacometabolism_original_article,10.1016/j.phrs.2025.107998,CC BY; not encoded in row-level synthetic tables,deferred_general_CYP_drug_metabolism_context,siRNA knockdown|primary human hepatocytes|NFI transcription factors|CYP activity|drug metabolism,general hepatic pharmacometabolism and hepatocyte-function context; lower direct relevance because therapeutic oligos are not mainly CYP-metabolized,deferred,Deferred from row-level generation to avoid diluting therapeutic oligo toxicity focus.,source_metadata,no,CC BY 4.0
TANG_CUPROPTOSIS_WILSON_DISEASE_2025,Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets,2025,copper_liver_injury_original_article,10.1111/jcmm.70946,CC BY; generated variables only; do not reproduce source figures/tables/text,supporting_cuproptosis_copper_induced_liver_injury_module,siRNA knockdown|ATP7B knockout|cuproptosis|copper overload|ALT|AST|LDH|HepG2|Wilson disease,"adds copper-dependent hepatocyte injury, regulated cell death, LDH/ALT/AST injury context, and siRNA rescue of cuproptosis mediators",yes_supporting_module,Useful for modeling non-oligo liver-injury stress axes and siRNA-validated rescue targets in copper-induced hepatotoxicity.,source_metadata,no,CC BY 4.0
SALIM_GALNAC_SIRNA_WB_PBPK_PD_2025,Whole-Body Physiologically Based Pharmacokinetic–Pharmacodynamic Modeling for Interspecies Translation and Mechanistic Characterization of Plasma and Tissue Disposition of GalNAc-siRNAs,2025,PBPK_PD_modeling_original_article,10.3390/pharmaceutics17091154,CC BY; generated variables only; do not reproduce source figures/tables/text,direct_GalNAc_siRNA_PK_PD_species_translation_and_off_target_distribution_module,GalNAc-siRNA|PBPK|PK-PD|ASGPR|RISC|mouse|monkey|human|off-target organs|liver exposure,"adds mechanistic GalNAc-siRNA disposition, cross-species scaling, liver specificity, off-target organ accumulation, and clinical PK-PD translation context",yes_supporting_module,High-value modeling rigor source for PK/PD and preclinical-to-clinical translation of GalNAc-siRNAs.,source_metadata,no,CC BY 4.0
VAILLANT_HBV_OLIGONUCLEOTIDE_THERAPIES_REVIEW_2022,"Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects",2022,review_open_access,10.3390/v14092052,CC BY; not encoded in row-level synthetic tables,deferred_review_background_for_HBV_oligonucleotide_mechanisms,ASO|siRNA|NAP|HBV|immunostimulation|GalNAc|LNP|liver uptake|off-target effects,"useful background on oligonucleotide pharmacology and HBV therapeutic classes, but review-only",deferred,Deferred from row-level generation to keep source-specific generated rows focused on primary studies and modeling papers.,source_metadata,no,CC BY 4.0
LACALAMITA_PID_MICROARRAY_HIGH_ORDER_PATTERNS_2025,Unveiling complex patterns: An information-theoretic approach to high-order behaviors in microarray data,2025,bioinformatics_methods_original_article,10.1371/journal.pone.0336379,CC BY; not encoded in row-level synthetic tables,deferred_optional_notebook_method_context,microarray|HCC|partial information decomposition|synergy clusters|mutual information|gene expression,general high-order gene-expression methods; not therapeutic oligo toxicity or delivery evidence,deferred,"Potentially useful later for an optional notebook method, but deferred from the core generator to avoid diluting OligoTox focus.",source_metadata,no,CC BY 4.0
AGARWAL_GALNAC_SIRNA_OFFTARGET_2025,Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates,2025,mechanistic_original_article_open_access,10.1089/nat.2024.0090,open access CC BY; generated variables only; do not reproduce source figures/tables/text,core_GalNAc_siRNA_RISC_AGO2_TNRC6_seed_offtarget_hepatotoxicity_module,GalNAc-siRNA|AGO2|AGO1|AGO4|TNRC6A|TNRC6B|TNRC6C|RISC|seed_offtarget|hepatotoxicity,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,yes_core_module,Final supplemental high-priority paper; encoded in off-target RISC mechanism table and used to refine seed/off-target hepatotoxicity logic.,source_metadata,no,CC BY 4.0
EGLI_MANOHARAN_APPROVED_OLIGO_CHEMISTRY_2023,"Chemistry, Structure and Function of Approved Oligonucleotide Therapeutics",2023,critical_review_open_access,10.1093/nar/gkad067,open access CC BY-NC; generated variables only; do not reproduce source figures/tables/text,core_reference_approved_oligonucleotide_chemistry_delivery_landscape_module,ASO|SSO|siRNA|aptamer|phosphorothioate|2prime_F|2prime_OMe|2prime_MOE|PMO|LNP|GalNAc,"core chemistry and delivery reference for approved oligonucleotide therapeutics, chemical modifications, LNPs, and GalNAc hepatocyte targeting",yes_core_reference_module,"Used to anchor chemistry/delivery categories, approved landscape context, and data dictionary terminology.",source_metadata,no,CC BY 4.0
ARMISEN_AZD2693_PNPLA3_ASO_MASH_2025,"AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: Two randomized phase I trials",2025,phase1_clinical_and_preclinical_original_article_open_access,10.1016/j.jhep.2024.12.046,open access CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,core_PNPLA3_GalNAc_ASO_precision_MASH_target_engagement_module,GalNAc-ASO|PNPLA3|MASH|148M_homozygous|liver_fat|hCRP|IL6|target_engagement|PK|PD,"direct precision hepatology source for liver-targeted ASO target engagement, MASH biomarkers, hepatic fat response, and safety/tolerability context",yes_core_module,Adds original PNPLA3 ASO clinical target-engagement evidence beyond the PNPLA3 review already represented.,source_metadata,no,CC BY 4.0
CROOKE_RNA_TARGETED_THERAPEUTICS_2018,RNA-Targeted Therapeutics,2018,perspective_article,10.1016/j.cmet.2018.03.004,freely downloadable PDF; generated variables only; do not reproduce source figures/tables/text,supporting_RNA_targeted_therapeutics_platform_mechanism_module,ASO|siRNA|Watson-Crick_hybridization|Ago2|RNase_H1|chemistry|delivery|structure_matters,"supporting platform source for ASO/siRNA structural, chemical, pharmacokinetic, and mechanism distinctions relevant to safety modeling",yes_supporting_platform_module,Used to encode broad platform distinctions between single-stranded ASOs and double-stranded siRNAs.,source_metadata,no,CC BY 4.0
OLIVER_HILL_MODEL_SELECTION_NAT_2026,Model Selection in Preclinical Nucleic Acid Therapeutics Research,2026,review_open_access,10.1038/s42003-026-09650-7,open access; generated variables only; do not reproduce source figures/tables/text,supporting_preclinical_model_selection_NAT_methods_module,ASO|siRNA|preclinical_models|surrogate_NAT|humanized_locus|patient_cells|in_vitro|in_vivo,"supports model-system selection, species/sequence alignment, surrogate versus humanized models, and interpretation of preclinical readouts",yes_supporting_methods_module,"Used to justify model_system, sequence_alignment, humanized_model, and surrogate_NAT metadata.",source_metadata,no,CC BY 4.0
ALSHAER_FDA_TIDES_HARVEST_2025,2025 FDA TIDES (Peptides and Oligonucleotides) Harvest,2026,review_open_access,10.3390/ph19020244,open access CC BY; generated variables only; do not reproduce source figures/tables/text,supporting_current_approved_oligonucleotide_landscape_module,approved_oligonucleotides|fitusiran|donidalorsen|plozasiran|GalNAc|subcutaneous|FDA_2025,current regulatory/approval landscape context; highlights continued clinical maturity of GalNAc hepatocyte-targeted oligonucleotide delivery,yes_supporting_landscape_module,Used for current approved oligonucleotide landscape and GalNAc trend context.,source_metadata,no,CC BY 4.0
ABULHUSN_HSD17B13_PROTECTIVE_VARIANT_2018,A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease,2018,human_genetics_original_article,10.1056/NEJMoa1712191,freely downloadable PDF; generated variables only; do not reproduce source figures/tables/text,core_HSD17B13_protective_human_genetics_target_rationale_module,HSD17B13|loss_of_function|ALT|AST|chronic_liver_disease|NASH|cirrhosis|PNPLA3_interaction|human_genetics,foundational human-genetics target rationale for HSD17B13 silencing strategies and liver-protection phenotypes,yes_core_module,Used to anchor HSD17B13 target rationale and protective liver phenotype variables.,source_metadata,no,CC BY 4.0
MA_HSD17B13_ASO_FIBROSIS_MOUSE_2024,Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model,2024,preclinical_original_article_open_access,10.1016/j.jlr.2024.100514,open access CC BY; generated variables only; do not reproduce source figures/tables/text,core_HSD17B13_ASO_preclinical_steatosis_fibrosis_limitations_module,Hsd17b13_ASO|LNA_gapmer|phosphorothioate|CDAHFD|NASH|steatosis|fibrosis|primary_hepatocytes,"preclinical ASO source showing Hsd17b13 knockdown, steatosis modulation, and fibrosis-response limitations in a diet-induced NASH-like fibrosis model",yes_core_module,Used to distinguish target knockdown and steatosis effects from lack of fibrosis improvement in a specific mouse model.,source_metadata,no,CC BY 4.0