metadata/source_triage_log.csv

decision,judging_use,license_or_access,module_added,phase2_fit,reason,source_id,source_type,title,triage_decision
,supports rigor/transparency by documenting why each source was used or deferred,DBbun-authored working memo,,,"Defines target tables, predictors, controls, provenance, and generation rules.",MEMO_OLIGOTOX_PHASE2_ALIGNMENT,alignment_memo,DBbun OligoTox Phase 2 Alignment Memo,include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,Creative Commons Attribution,,,"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.",PNPLA3_ROMEO_VALENTI_2025,review_open_access,Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",RAPIROSIRAN_SANYAL_2025,phase1_randomized_double_blind_clinical_open_access,Phase I randomized double-blind study of an RNA interference therapeutic targeting HSD17B13 for metabolic dysfunction-associated steatohepatitis,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,Creative Commons Attribution,,,"Adds long-term human liver spheroid model, GalNAc uptake, durability, PS backbone variation, and human-relevant in vitro context.",LIVER_SPHEROID_SCHOLTEN_2026,human_in_vitro_open_access,A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs,include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"Adds ASO clinical safety, PK/PD, liver uptake saturation concept, and transaminase-related toxicity signals.",RO7239958_GERETTI_2025,phase1_clinical_open_access,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,,,"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.",MOHAMED_NANOPARTICLE_HEPATITIS_2026,review_open_access_restricted_reuse,Nanoparticle approaches for hepatitis therapy and clinical translation,include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,,,"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.",MENG_HYBRID_RNA_LNP_HCC_2025,research_open_access_restricted_reuse,Reversal of tumour immune evasion via enhanced MHC-Class-I antigen presentation by a dual-functional RNA regulated system,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",CHEN_OVARIAN_MTTP_APOB_MIPOMERSEN_2025,research_open_access,Ovarian expression of functional MTTP and apoB for VLDL assembly and secretion in chickens,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,,,"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.",LU_SULT1B1_SE_MASLD_2026,research_open_access_restricted_reuse_article_in_press,Super-enhancer-driven recruitment of C/EBPbeta by SULT1B1 is implicated in metabolic dysfunction-associated steatotic liver disease progression,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,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.,OOSTVEEN_ANGPTL3_LIVER_SAFETY_2023,review_open_access,Angiopoietin-like 3 inhibition and the liver: less is more?,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",ENGELBEEN_ALK4_MUSCLE_SIRNA_2023,research_open_access,Efficient Downregulation of Alk4 in Skeletal Muscle After Systemic Treatment with Conjugated siRNAs in a Mouse Model for Duchenne Muscular Dystrophy,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,NEJM copyrighted article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",KIM_MILASEN_CUSTOM_ASO_2019,n_of_1_clinical_brief_report,Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",KEATING_ASO_OBESITY_NAFLD_2022,mini_review_open_access,Antisense Oligonucleotide Technologies to Combat Obesity and Fatty Liver Disease,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,Mary Ann Liebert open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",HAGEDORN_LNA_HEPATOTOX_RF_2013,research_open_access,Hepatotoxic Potential of Therapeutic Oligonucleotides Can Be Predicted from Their Sequence and Modification Pattern,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt source figures/tables/text,,,"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.",GANE_VIR2218_ALNHBV_HBV_RNAI_2023,preclinical_and_randomized_clinical_open_access_restricted_reuse,Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,review_open_access,Zilebesiran—Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,,,"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.",HAUPTMANN_SIRNA_BULGES_GALNAC_2022,mechanistic_siRNA_design_open_access_restricted_reuse,Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,HCC_multiomics_spatial_transcriptomics_functional_siRNA_open_access,Integrated Multi-Omics and Spatial Transcriptomics Identify FBLL1 as a Malignant Transformation Driver in Hepatocellular Carcinoma,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,GalNAc_LNP_siRNA_liver_regeneration_open_access,Dual targeted gene delivery strategy mediated by GalNAc-modified lipid nanoparticles enhances liver regeneration through specific knockdown of MKK4,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce or adapt figures/tables/text,,,"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.",WANG_OGT_SEV_LSEC_MASLD_2026,research_open_access_restricted_reuse,OGT-enriched Hepatocyte-derived Extracellular Vesicles Promote Capillarization of Liver Sinusoidal Endothelial Cells in Metabolic Dysfunction-associated Steatotic Liver Disease,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; use as evidence/context; original article not redistributed,,,"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.",DU_MALAT1_HBV_HCC_ASO_2025,research_open_access,MALAT1 promotes malignancy of HBV-related hepatocellular carcinoma by regulating IGF2BP3-mediated nuclear-cytoplasmic shuttling,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; use as evidence/context; original article not redistributed,,,"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.",PAN_CD133_MASLD_HCC_SIRNA_2025,research_open_access_restricted_commercial_reuse,Targeting cancer stem cells enhances multikinase inhibitor therapy in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; use as evidence/context; original article not redistributed,,,"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.",HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,research_open_access_restricted_commercial_reuse,Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",KARTOUN_MELD_PLUS_CIRRHOSIS_2017,clinical_prediction_model_open_access,The MELD-Plus: A generalizable prediction risk score in cirrhosis,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,open_access_CC_BY_NC_ND,,,"ALDH2 activity, acetaldehyde detoxification, ROS/lipid peroxidation, mitochondrial function, ERK1/2-Nrf2 antioxidant signaling, and AAV8 siRNA loss-of-rescue controls.",MA_FORMONONETIN_ALDH2_ALD_2025,research_article_supporting_liver_context,Formononetin mitigates alcoholic liver disease by restoring ALDH2 function and inducing ERK1/2–Nrf2 antioxidant signaling,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open_access_CC_BY,,,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.,VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,research_article_supporting_siRNA_nanoparticle_safety_context,In Vivo HOXB7 Gene Silencing and Cotreatment with Tamoxifen for Luminal A Breast Cancer Therapy,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open_access_CC_BY,,,"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.",WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,research_article_supporting_sEV_small_RNA_delivery_context,Robust loading and delivery of functional small RNAs via protein N-myristoylation-induced small extracellular vesicles,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,NCBI_Bookshelf_methods_chapter_context_only,,,"Used to strengthen safety-assessment variables, controls, and provenance; source text/figures are not redistributed.",ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,methods_chapter_preclinical_safety_review,Preclinical Safety Assessment of Therapeutic Oligonucleotides,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,journal_pdf_user_provided; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",BI_IFNA_DISULFIDPTOSIS_HCC_2026,mechanistic_cell_study_liver_cancer,Interferon-alpha induces disulfidptosis occurrence in human liver cancer cells,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,SAGE article user_provided; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",JANAS_GALNAC_RNAI_NONCLINICAL_SAFETY_2018,review_platform_nonclinical_safety,The Nonclinical Safety Profile of GalNAc-conjugated RNAi Therapeutics in Subacute Studies,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",BOSCO_INCLISIRAN_FH_REALWORLD_2025,clinical_real_world_observational_inclisiran,Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0,,,"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.",DEBACKER_GALNAC_LIVER_DELIVERY_REVIEW_2020,review_GalNAc_liver_delivery_clinical_translation,Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open access; user-provided PDF; cite source but do not reproduce full tables/figures/text,,,"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.",RANASINGHE_SIRNA_PHARMACOLOGY_REVIEW_2023,review_siRNA_discovery_pharmacology_clinical_development,"Small interfering RNA: Discovery, pharmacology and clinical development — An introductory review",include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0,,,"Adds positive/negative ASO gapmer controls, acute 3-day screen proxies, repeat-dose concordance, OTE count, transcriptome selectivity, ALT/AST and liver-weight endpoints.",KAMOLA_ASO_HEPATOTOX_SCREEN_2017,peer_reviewed_open_access_article,Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs,include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,bioRxiv preprint; author/funder copyright notice says no reuse without permission; use as evidence/context only; do not redistribute source text or figures,,,"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.",LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,bioRxiv_preprint_not_peer_reviewed,Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,bioRxiv preprint; author/funder copyright notice says no reuse without permission; use as evidence/context only; do not redistribute source text or figures,,,"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.",WEISS_GYS1_ASO_POMPE_PREPRINT_2024,bioRxiv_preprint_not_peer_reviewed,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,Creative Commons Attribution CC-BY 4.0; use as source evidence/context only; do not redistribute source PDF/figures in generated package,,,"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.",OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,peer_reviewed_research_article,Dynamic cholangiocyte responses in a murine model of reversible cholestasis: macrophage remodeling and NF-Y-mediated TGFβ1 expression,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,"Springer Nature exclusive licence; use as source evidence/context only; do not redistribute source PDF, figures, tables, sequences, or long source text",,,"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.",KANDA_PCDHA11_AMNA_ASO_2024,peer_reviewed_preclinical_therapeutic_ASO_study,Dual-modified antisense oligonucleotides targeting oncogenic protocadherin to treat gastric cancer,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,Nature Communications open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",HJELMGREN_PS_ASO_DDR_2026,mechanistic_ASO_toxicity_open_access,Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,Nature Communications open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",LAN_SIRUBICON_ROS_GALNAC_MASH_2025,preclinical_liver_siRNA_delivery_open_access,Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated chemistry-safety variables for scpBNA/scpBNA2 substitution, reduced PS burden, retained knockdown, nuclease stability, and lower ALT/AST.",YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,ASO_chemistry_hepatotoxicity_open_access,"Cycloalkane Incorporation Into the 2′,4′-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated APAP acute liver injury context, si-Cyp2e1 LNP knockdown, timing, ALT/AST, necrosis, oxidative stress, inflammatory cytokines, and recovery variables.",LIU_CYP2E1_LNP_APAP_AILI_2025,preclinical_RNAi_LNP_DILI_open_access,Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated NANP design variables for ligand valency, lipid chemistry, ApoE/LDLR/SR-B1 engagement, hepatocyte uptake, LSEC/Kupffer association, and immunotoxicity monitoring.",KIM_NANP_LIPID_LIVER_TARGETING_2026,nucleic_acid_nanoparticle_delivery_open_access,Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated RNA nanoparticle variables for multitarget RNAi in Hep3B cells, liver-cancer xenograft context, proliferation/migration/apoptosis, and off-target toxicity monitoring.",SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,RNA_nanoparticle_liver_cancer_open_access,Design of Anti-Tumor RNA Nanoparticles and Their Inhibitory Effect on Hep3B Liver Cancer,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated asymmetric-siRNA design variables: reduced seed/off-target risk, DCA conjugation, VP modification, long-duration knockdown, and visible-toxicity monitoring.",MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,asymmetric_siRNA_design_delivery_safety_open_access_noncommercial,"Design, Screening and Development of Asymmetric siRNAs Targeting the MYC Oncogene in Triple-Negative Breast Cancer",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/sequences verbatim,,,"Adds generated HDO multifunctionalization variables for targeted intracellular delivery, dual ligand labeling, GFP/BCL2 silencing context, and non-liver off-target framing.",SOUSA_HDO_MULTIFUNCTIONAL_HELA_2022,HDO_intracellular_delivery_open_access,Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; evidence/context only; generated variables only; no source schemes reproduced,,,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.,KUMAGAI_SCPBNA2_PURINE_SYNTHESIS_2025,ASO_chemistry_synthesis_open_access,"Development of Synthetic Routes to 2-O,4-C-Spirocyclopentylene-Bridged Nucleic Acids: Thymidine, Guanosine, and Adenosine",deferred
,supports rigor/transparency by documenting why each source was used or deferred,user-provided PDF; text extraction limited/garbled; context only until manually reviewed,,,Deferred from code-module integration in v1.0 because extracted text was not reliable enough for rigorous source-grounded variable design.,BJD_BMP1_SHRNA_AAV_CCL4_FIBROSIS_CONTEXT,shRNA_AAV_liver_fibrosis_context_user_pdf_text_extraction_limited,Protective effect of knockdown Bmp1 gene on carbon tetrachloride-induced liver fibrosis in mice,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; evidence/context only; generated variables only; no source figures/tables/sequences reproduced,,,"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.",HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,therapeutic_siRNA_design_pharmacology_toxicology_open_access_restricted_reuse,"Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,,,"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.",QU_CPG_ODN_APAP_TLR9_IRG1_2025,CpG_ODN_APAP_liver_injury_open_access,CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC 4.0; generated variables only; no source figures/tables reproduced,,,"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.",PARK_ERBB2_APTAMER_PET_PK_2023,aptamer_tissue_PK_PET_open_access_noncommercial,In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open access; evidence/context only; generated variables only if later promoted,,,"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.",XI_HCC_CHROMATIN_DGAT1_SIRNA_2025,single_cell_HCC_epigenomics_siRNA_validation_open_access,Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; evidence/context only; generated variables only if later promoted,,,"Deferred from v1.0 full module: useful autoimmune liver-injury network context, but not directly about therapeutic oligos, chemical modifications, delivery, or oligo toxicity.",LI_AIH_CERNA_NETWORK_2022,autoimmune_hepatitis_ceRNA_network_open_access,Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis,deferred
,supports rigor/transparency by documenting why each source was used or deferred,open access; generated variables only; no source figures/tables/sequences reproduced,,,"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.",TERADA_BROTHERS_ASO_PNA_TOEHOLD_2023,direct_ASO_hepatotoxicity_mitigation_mechanism_open_access,Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; generated variables only; no source figures/tables/sequences reproduced,,,"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.",PRAKASH_APOC3_LONG_ACTING_GALNAC_SIRNA_2025,direct_GalNAc_siRNA_SAR_duration_tolerability_open_access_noncommercial,Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; generated variables only; no source figures/tables reproduced,,,"Adds analytical rigor variables: sample-prep recovery, matrix interference, LLOQ, metabolite distinction, approved GalNAc-siRNA comparators, and rat-plasma PK support.",KIM_GALNAC_SIRNA_LCMS_DPPT_2025,GalNAc_siRNA_bioanalysis_LCMS_method_open_access_restricted_reuse,Differential Protein Precipitation-Based GalNAc-siRNA Sample Preparation with LC/MS Method Development Workflow in Plasma,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; generated variables only; no source figures/tables/sequences reproduced,,,"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.",UMEZU_ORAL_MIR29A_LIVER_FIBROSIS_NA_2025,modified_miRNA_like_liver_fibrosis_therapy_open_access_restricted_reuse,Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; evidence/context only; generated variables only if later promoted,,,"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.",LU_GT_MULTI_SIRNA_HCC_2025,branched_multi_siRNA_HCC_open_access,Development of a Dual Gene-Targeted Multi-Sirna with Branched Structure and Its Role in the Therapy of Liver Cancer,deferred
,supports rigor/transparency by documenting why each source was used or deferred,open access but publisher reserves text/data mining and AI training rights; generated variables only; no source figures/tables/sequences reproduced,,,"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.",JIANG_LNP_CRISPR_HAO1_PH1_2025,liver_targeted_LNP_CRISPR_Cas9_long_term_safety_open_access_restricted_text_mining,Efficient and safe in vivo treatment of primary hyperoxaluria type 1 via LNP-CRISPR-Cas9-mediated glycolate oxidase disruption,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; no source figures/tables/sequences reproduced,,,"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.",GOTFRID_PS_LNA_HIV_ASO_ACTIVITY_2026,PS_and_PS_LNA_ASO_activity_internalization_toxicity_open_access,Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; evidence/context only; generated variables only if later promoted,,,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.,XU_FGF21_MAPK1_DAIRY_KETOSIS_SIRNA_2025,bovine_liver_lipid_metabolism_siRNA_functional_context,FGF21-MAPK1 Imbalance Disrupts Hepatic Lipid Metabolism in Dairy Cow Ketosis,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; 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.,ELGHAZZI_GENE_SILENCING_GI_GU_TUMORS_REVIEW_2025,review_gene_silencing_oncology_context,"Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors",deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; 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.,YANG_PIRNA_CANCER_DIAGNOSTIC_THERAPEUTIC_REVIEW_2026,review_piRNA_cancer_context,Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; generated variables only; no source figures/tables/sequences reproduced,,,"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.",SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,direct_GalNAc_siRNA_offtarget_hepatotoxicity_mitigation_primary_mechanistic_translation,From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; no source figures/tables/sequences reproduced,,,"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.",DHARA_LNA_PHOSPHOTHIOTRIESTER_SSO_CLICK_2025,modified_oligonucleotide_backbone_biophysical_splice_switching_primary_chemistry,Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,,,"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.",LI_FXR_JNK_G0S2_TRIPTOLIDE_HEPATOTOXICITY_2025,drug_induced_liver_injury_metabolic_pathway_siRNA_mechanism_primary,FXR as a pivotal role linking JNK and G0s2 mitigates triptolide-induced hepatotoxicity through the regulation of metabolic disorder of liver,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; context only unless later promoted,,,"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.",JEON_COP1_HCC_LIPID_STEMNESS_SIRNA_2026,HCC_siRNA_lipid_metabolism_context,Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness,deferred
,supports rigor/transparency by documenting why each source was used or deferred,duplicate of source SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,,,"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.",SCHLEGEL_GKAC539_DUPLICATE_UPLOAD_2022,duplicate_upload_not_integrated_separately,Duplicate upload of From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; no source figures/tables/sequences reproduced,,,"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.",BUREL_GAPMER_RNASEH1_LONG_PREMRNA_HEPATOTOX_2016,direct_ASO_gapmer_hepatotoxicity_mechanism_primary_transcriptomics,Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; generated variables only; no source figures/tables/text reproduced,,,"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.",JIANG_AOC_FREE_ASO_PAYLOAD_HYBRIDIZATION_LCMS_2024,ASO_bioanalysis_PK_PD_measurement_primary_method,Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; no source figures/tables/text reproduced,,,"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.",WAN_PUM1_EXOSOMES_MASLD_HSC_FIBROSIS_2025,MASLD_liver_fibrosis_exosome_RNA_binding_shRNA_siRNA_primary,Hepatocyte-derived Pumilio1-enriched exosomes inhibit HSC activation by suppressing tropomyosin-4 translation,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; context only unless later promoted,,,"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.",ZHU_HMMR_HCC_4MU_SIRNA_2026,HCC_target_validation_siRNA_context,HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; review context only unless later promoted,,,"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.",GHOLIKHANI_APTAMER_BREAST_CANCER_REVIEW_2022,aptamer_review_context_only,"Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics",deferred
,supports rigor/transparency by documenting why each source was used or deferred,open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds clinical ASO biomarker layer for interpreting ALT increases, infected-hepatocyte killing, HBsAg decline, immune activation, and transcript/protein timing.",JOSHI_BEPIROVIRSEN_B_TOGETHER_IMMUNOMODULATION_2026,clinical_biomarker_original_article,Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study),include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds serinol nucleic acid ASO chemistry, systemic delivery, kidney uptake, duration, glucosuria PD, and liver-safety comparison against MOE-ASO context.",TSUBOI_SNA_ASO_SGLT2_KIDNEY_SYSTEMIC_SAFETY_2025,preclinical_original_article,In vivo efficacy and safety of systemically administered serinol nucleic acid-modified antisense oligonucleotides in mouse kidney,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds p-LNP endosomal escape, liver expression, siRNA ED50 improvement, RNA stability, pH buffering, and no significant liver toxicity context.",KANNAN_POLYAMINE_PLNP_RNA_DELIVERY_SAFETY_2025,delivery_platform_original_article,Incorporation of a polyamine into lipid nanoparticles increases the endosomal release and transfection of nucleic acids without toxicity,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred from core generation,,,"Useful liver metabolism/omics background, but peptide/obesity focused and not sufficiently oligonucleotide-toxicity-specific for a new core module.",TAKENOYA_GALP_HFD_LIVER_TRANSCRIPTOME_METABOLOME_2023,liver_omics_original_article,Transcriptomic and metabolome analyses of liver in high-fat diet mice after intranasal GALP,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access review; deferred from core generation,,,"Broad review useful for narrative/background, but not used as a primary data-generating module to avoid review-only signal inflation.",SHEVELEV_SIRNA_THERAPEUTICS_REVIEW_2025,review,siRNA therapeutics for the treatment of hereditary diseases and other conditions: A review,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",VAN_LEEUWEN_ASO_MULTIOMICS_TIME_RESOLVED_SAFETY_2026,ASO_multiomics_original_article,Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",RIDER_SLN360_LPA_GALNAC_SIRNA_PRECLINICAL_TOX_2022,preclinical_toxicology_original_article,"Preclinical Toxicological Assessment of A Novel siRNA, SLN360, Targeting Elevated Lipoprotein(a) in Cardiovascular Disease",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds Kupffer-cell biomimetic nanoparticle delivery, BRCC3 siRNA, NLRP1 inflammasome biology, LPS/CLP sepsis-related liver injury context, and liver-enrichment/targeted uptake variables.",MA_KUPFFER_BIOMIMETIC_ZIF8_BRCC3_SIRNA_SRLI_2025,nanomedicine_siRNA_original_article,Kupffer cells biomimetic nanoparticles alleviate sepsis related liver injury,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred from core generation,,,"Potentially useful ASO splice-correction context, but deferred because it has limited direct oligo toxicity, liver enzyme, or hepatotoxicity prediction signal.",LI_PKHD1_ARPKD_ASO_SPLICE_RESCUE_2023,ASO_splicing_original_article_deferred,A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND open-access article; deferred from core generation,,,"Useful liver-disease genetic diagnostics context, but not a therapeutic oligo toxicity source and therefore not used for new core rows.",JIA_ATP7B_WILSON_MICROARRAY_DIAGNOSTIC_2022,diagnostic_microarray_original_article_deferred,Laboratory and clinical evaluation of a microarray for the detection of ATP7B mutations in Wilson disease in China,deferred
,supports rigor/transparency by documenting why each source was used or deferred,publisher article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",BAI_EZH2_EXON_SKIPPING_HCC_ASO_2025,splice_switching_ASO_liver_cancer_original_article,Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",KABURAGI_TOC_HDO_DRG_SCIATIC_SYSTEMIC_DELIVERY_2022,HDO_ASO_delivery_original_article,Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds HSC activation, XIST knockdown, miR-663a/GPX4 ferroptosis axis, ALT/AST/HYP liver injury markers, and fibrosis rescue/antagonist logic.",DAI_XIST_MIR663A_GPX4_HSC_FERROPTOSIS_FIBROSIS_2026,lncRNA_siRNA_shRNA_liver_fibrosis_original_article,Long noncoding RNA X-inactive-specific transcript promotes hepatic fibrosis by suppressing ferroptosis in hepatic stellate cells via the miR-663a/GPX4 axis,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred from core oligo generation,,,"Useful liver-targeting comparator and fibrosis biology source, but deferred because the active therapeutic is a GalNAc-PROTAC rather than an oligonucleotide.",YUAN_LIVTAC_GALNAC_PROTAC_BRD4_FIBROSIS_2025,liver_targeted_GalNAc_PROTAC_original_article_deferred,Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred from core generation,,,"Contains useful ALT/AST/TG and PPAR-alpha siRNA pathway context, but deferred because the therapeutic intervention is polysaccharide/nutraceutical rather than oligo-centric.",CAI_LYCIUM_POLYSACCHARIDES_ETHANOL_LIVER_INJURY_2025,hepatoprotection_original_article_deferred,Lycium barbarum Polysaccharides Alleviate Ethanol-Induced Liver Injury by Activating PPAR-alpha and Inhibiting NLRP-3/Caspase-1-Mediated Pyroptosis,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",LIN_GALNAC_SICIDEB_MASH_STEATOSIS_FIBROSIS_2025,GalNAc_siRNA_MASH_original_article,Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,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.,KURODA_ASO_LATE_ONSET_NEUROTOX_5CP_MODIFICATIONS_2025,ASO_CNS_toxicity_chemical_modification_original_article,Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"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.",KHORSANDI_GALNAC_SICEBPB_MASLD_HOMEOSTASIS_2026,GalNAc_siRNA_MASLD_original_article,GalNAc-conjugated siRNA targeting C/EBPbeta reverses metabolic dysfunction and restores liver homeostasis in a murine MASLD model,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds non-liposomal trivalent disulfide-unit delivery chemistry, cellular uptake, thiol-blocking dependence, low cytotoxicity, and rapid liver distribution context.",WANG_TRIVALENT_DISULFIDE_MASKED_ODN_DELIVERY_2024,oligonucleotide_delivery_chemistry_original_article,Trivalent Disulfide Unit-Masked System Efficiently Delivers Large Oligonucleotide,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,freely accessible article; deferred from oligo toxicity generator,,,"Deferred because it is a lung-cancer survival-marker study without therapeutic oligonucleotide toxicity, liver-safety, delivery, or oligo chemistry relevance.",NASTASE_NSCLC_LONG_TERM_SURVIVAL_MARKERS_2022,cancer_genomics_microarray_WES_article_deferred,Molecular Markers for Long-term Survival in Stage IIIA (N2) NSCLC Patients,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND 4.0; use as evidence/context only; do not reproduce/adapt source figures/tables/text,,,"Adds Ox-mtDNA, mPTP, ITPR3/Ca2+/NLRP3, macrophage pyroptosis, ALT/AST, MASH progression, siRNA/AAV perturbation context.",ZHANG_MPTP_OXMTDNA_MASH_ITPR3_NLRP3_2025,primary_research_open_access,MPTP mediated Ox-mtDNA release inducing macrophage pyroptosis and exacerbating MCD-induced MASH via ITPR3/Ca2+/NLRP3 pathway,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds Cspg4/NG2 siRNA, fibrotic liver models, myofibroblast differentiation, collagen, ALT/AST, steatosis and inflammation improvement context.",YANG_NG2_CSPG4_SIRNA_LIVER_FIBROSIS_2023,primary_research_open_access,Neuron-Glial Antigen 2 participates in liver fibrosis via regulating BMSC differentiation to myofibroblast,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,publisher manuscript; use as evidence/context only; do not reproduce source figures/tables/text,,,"Adds high-throughput in vivo LNP screening, DNA barcode readout, HNSCC delivery, and minimized off-target liver hepatocyte delivery context.",HUAYAMARES_HNSCC_LNP_TUMOR_TROPISM_LIVER_DETARGET_2023,primary_research_manuscript,High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,"CC BY 4.0; review-only; use for narrative/context, not core generated table",,,Review source useful for background but not added as a source-specific generation module to avoid review-only noise.,HUANG_NANOPARTICLE_SIRNA_ONCOLOGY_REVIEW_2022,review_open_access,Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic siRNA in Precision Oncology,deferred
,supports rigor/transparency by documenting why each source was used or deferred,"author manuscript/review; use for narrative/context, not core generated table",,,Review source useful for final narrative/license/background but not added as a source-specific generated table.,RUCHI_EVOLUTION_ASO_CHEMISTRY_DELIVERY_REVIEW_2025,review_author_manuscript,Evolution of Antisense Oligonucleotides: Navigating Nucleic Acid Chemistry and Delivery Challenges,deferred
,supports rigor/transparency by documenting why each source was used or deferred,author manuscript/open access via PMC; use as evidence/context only,,,Adds systemic ASO versus selective siRNA contrast and macrophage immunometabolism context.,SINHA_NNMT_ASO_MACROPHAGE_ATHEROSCLEROSIS_2025,ASO_siRNA_immunometabolism_original_article,NAD metabolism regulates proliferation of macrophages in atherosclerosis,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only,,,"Adds oral RNA delivery, C2 micelle protection, macrophage/monocyte exposure, and tolerability/liver-enzyme context.",YAMAGUCHI_TY1_ORAL_NCRNA_MACROPHAGE_C2_2025,oral_ncRNA_delivery_original_article,"Oral Bioavailability of a Noncoding RNA Drug, TY1, That Acts on Macrophages",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; use as evidence/context only,,,"Adds non-cationic siRNA carrier, RNase protection, endosomal escape, tumor targeting, and low-toxicity delivery context.",YU_DUAL_RGD_DSRBD_18HIS_TUMOR_SIRNA_DELIVERY_2021,siRNA_delivery_nanocarrier_original_article,Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred,,,"Deferred because it is lentiviral shRNA cartilage repair, not an oligo hepatotoxicity dataset source.",LARIJANI_P21_SHRNA_CARTILAGE_REPAIR_2026,lentiviral_shRNA_cartilage_original_article_deferred,p21 Knockdown as a Therapeutic Strategy for Focal Cartilage Injury Repair,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY open-access article; deferred,,,"Deferred because siRNA is mechanistic, not the therapeutic modality.",THONGSRI_PANDURATIN_A_HBV_HNF1A_2026,small_molecule_HBV_liver_model_article_deferred,Panduratin A suppresses hepatitis B virus by targeting HNF1alpha,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; no commercial reuse; deferred context-only source,,,Deferred because the intervention is a small-molecule PIKfyve inhibitor; siRNA is used to validate mechanism rather than as therapeutic oligo modality.,RING_PIKFYVE_APILIMOD_HEV_ENTRY_2026,host_directed_HEV_antiviral_original_article_deferred,Phosphoinositide kinase PIKfyve inhibitor apilimod blocks hepatitis E virus infection,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; review-only deferred context source,,,Deferred because review-only sources are reserved for narrative/background rather than row-level generation.,SADDIQUE_RNAI_CARDIAC_FAILURE_SYSTEMATIC_REVIEW_2024,RNAi_cardiac_failure_systematic_review_deferred,Safety and effectiveness of interference RNA based therapeutics in cardiac failure: A systematic review,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; source used as scientific context/provenance only,,,Adds antisense LNA GapmeR targeting of a noncoding pseudogene in ovarian cancer preclinical models without evident toxicity.,RAMESH_KUMAR_RPSAP52_LNA_GAPMER_OVARIAN_PDOX_2025,LNA_GapmeR_lncRNA_pseudogene_original_article,Specific targeting of the pseudogene RPSAP52 reduces ovarian tumor growth in patient-derived orthoxenograft models,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,Elsevier/Molecular Therapy article; source used as scientific context/provenance only; do not redistribute source figures/tables/text,,,"Adds biological nanoparticle/hybrid nanovesicle RNA loading, targeting, intracellular delivery, and liver-targeted siRNA delivery context.",KOSTYUSHEVA_BIOLOGICS_HYB_TARGETED_RNA_DELIVERY_2025,biologics_based_RNA_delivery_original_article,Biologics-based technologies for highly efficient and targeted RNA delivery,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND; review-only deferred context source,,,Deferred from generated source tables because it is a review; useful later for final narrative and clinical context.,BHATIA_PELACARSEN_LPA_ASO_REVIEW_2025,clinical_ASO_review_deferred,Pelacarsen: Mechanism of action and Lp(a)-lowering effect,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; deferred source used as context only,,,"Deferred because the core intervention is transient CRISPR-Cas9 delivery, not oligo toxicology.",BARON_ALPHA_GAG_MS2_CRISPR_RNA_DELIVERY_2022,CRISPR_RNA_delivery_original_article_deferred,Improved alpharetrovirus-based Gag.MS2 particles for efficient and transient delivery of CRISPR-Cas9 into target cells,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; deferred source used as context only,,,"Deferred because it is diagnostics/machine-learning background, not oligo toxicity or delivery.",MADILL_HALLORAN_MMDX_TRANSPLANT_DIAGNOSTICS_2024,transplant_molecular_diagnostics_review_deferred,Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope Diagnostic System,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; do not reproduce source figures/tables/text,,,Adds direct GalNAc-siRNA hepatocyte-targeting and host-factor protection context.,STEEL_CD81_GALNAC_SIRNA_MALARIA_PROTECTION_2025,GalNAc_siRNA_liver_prophylaxis_original_article,Protection from malaria infection using liver-targeted siRNA,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; do not reproduce source figures/tables/text,,,Adds hepatocyte innate immune-response context relevant to oligo safety modeling.,LI_RBM39_HEPATOCYTE_IFN_INNATE_IMMUNITY_2025,hepatocyte_innate_immunity_original_article,RBM39 shapes innate immunity by controlling the expression of key factors of the interferon response,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; do not reproduce source figures/tables/text,,,"Adds GalNAc-siRNA sequence design, liquid-phase conjugation, comparator, and scalable synthesis context.",DMITRIEV_GALNAC_SIRNA_PCSK9_LIQUID_PHASE_2026,GalNAc_siRNA_design_synthesis_original_article,Refined Design and Liquid-Phase Assembly of GalNAc-siRNA Conjugates: Comparative Efficiency Validation in PCSK9 Targeting,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds HSC-specific LARP6 knockdown, collagen mRNA/translation regulation, fibrosis attenuation, and human liver spheroid context.",KIM_LARP6_HSC_FIBROSIS_DSI_RNA_2026,human_liver_fibrosis_dsiRNA_original_article,RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds RNAi-based transgene rheostat, reversible silencing, and liver AAV expression control context.",SUBRAMANIAN_RNAI_RHEOSTAT_AAV_TRANSGENE_2023,RNAi_transgene_control_original_article,RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; deferred source used as context only,,,Deferred because it is a review. Useful for final narrative but not row-level generated data.,FRIEDRICH_AIGNER_THERAPEUTIC_SIRNA_REVIEW_2022,siRNA_review_deferred,Therapeutic siRNA: State-of-the-Art and Future Perspectives,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds dedicated mechanistic off-target hepatotoxicity and mitigation table, complementary to prior platform safety context.",JANAS_GALNAC_SIRNA_OFFTARGET_RAT_HEPATOTOX_2018,GalNAc_siRNA_hepatotoxicity_mechanism_original_article,Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds toxicogenomics and ML validation context for DILI risk modeling, not oligo-specific but highly relevant to hepatotoxicity prediction rigor.",BERGEN_DILIMAP_TOXPREDICTOR_DILI_2025,DILI_toxicogenomics_original_article_supporting,A large-scale human toxicogenomics resource for drug-induced liver injury prediction,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds clinical single-stranded LNA ASO PK/PD, ASGPR uptake saturation, PAPD5/7 knockdown predictions, and transaminase-safety boundary context.",GERETTI_RO7239958_GALNAC_LNA_ASO_HBV_PHASE1_2025,clinical_GalNAc_LNA_ASO_phase1_original_article,"Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds aerosolized HNP/TGFb1 siRNA, mucus-barrier penetration, macrophage uptake, endosomal escape, and fibrosis-repair context.",LIU_HYDROGEN_HNP_TGFB1_SIRNA_PULMONARY_FIBROSIS_2025,inhaled_siRNA_delivery_original_article,Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,standard/open access metadata; generated variables only; do not reproduce source figures/tables/text,,,Adds PCSK9 siRNA as an immune-modulatory safety lever for STING agonist therapy and liver-vs-tumor toxicity boundary context.,SUN_PCSK9_SIRNA_STING_CANCER_IMMUNOTHERAPY_2025,PCSK9_siRNA_STING_immunotherapy_original_article,Silencing PCSK9 reshapes the spatiotemporal activation of STING for safe and effective cancer immunotherapy,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open access; deferred source used as 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.",XIE_TOP2A_HCC_SCRNA_SIRNA_KNOCKDOWN_2025,HCC_siRNA_knockdown_biology_deferred,Single cell-RNA sequencing reveal TOP2A as a key driver of hepatocellular carcinoma progression,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds systemic PS/cEt gapmer ASO targeting Gys1, skeletal-muscle glycogen reduction, ERT combination, and extrahepatic tissue-safety context.",WEISS_GYS1_ASO_POMPE_SKELETAL_MUSCLE_2025,ASO_skeletal_muscle_original_article,Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds LNP-mediated Sptlc2 siRNA, hepatocyte delivery, de novo ceramide pathway inhibition, MCD/CD-HFD MASH models, ALT/AST and fibrosis context.",YU_SPTLC2_LNP_SIRNA_MASH_CERAMIDE_2025,LNP_siRNA_MASH_original_article,Targeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds aptamer-siRNA selective binding/internalization, CD47 knockdown, PD-L1 targeting, Treg depletion, CD8 infiltration, and HCC antitumor context.",ZENG_PDL1_APTAMER_CD47_SIRNA_TREG_HCC_2025,aptamer_siRNA_chimera_HCC_immunotherapy_original_article,Targeting tumor-infiltrating regulatory T cells: combining CD47 and PD-L1 inhibition via a novel aptamer-siRNA chimera,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; generated variables only; do not reproduce source figures/tables/text,,,"Adds radiation liver injury, THBS1 biomarker, proteomics, collagen deposition, and siRNA knockdown reversal of fibrotic signaling.",WANG_THBS1_RILI_PROTEOMICS_SIRNA_2025,radiation_induced_liver_injury_proteomics_siRNA_original_article,THBS1 as a candidate biomarker and fibrotic mediator in radiation-induced liver injury,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; deferred source used as context only,,,Deferred because the study is dairy-cow ketosis biology and siRNA is a mechanistic perturbation tool rather than therapeutic oligo modality.,LIU_NEDD4_NEFA_KETOTIC_COW_LIVER_2026,bovine_ketosis_liver_injury_siRNA_mechanistic_deferred,The E3 ubiquitin ligase NEDD4 protects against nonesterified fatty acid-induced hepatic inflammatory injury in ketotic cows,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY 4.0; deferred source used as context only,,,Deferred because it is a bovine ketosis metabolism study; siRNA is target-validation rather than therapeutic oligo evidence.,CHEN_HNF4A_KETOTIC_COW_HEPATOCYTE_SIRNA_2025,bovine_ketosis_hepatocyte_siRNA_mechanistic_deferred,The hepatic expression status of hepatocyte nuclear factor 4alpha in subclinical and clinical ketotic dairy cows and its impact on lipid metabolism in hepatocytes,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC; generated variables only; do not reproduce source figures/tables/text,,,Useful for modeling cholestatic liver-injury mechanisms and cytoskeletal stress/apoptosis readouts relevant to hepatotoxicity.,TATSUKAWA_TG_KERATIN_BILE_ACID_HEPATOCYTE_DEATH_2025,cholestatic_liver_injury_original_article,Transglutaminase-mediated cytokeratin modifications implicated in bile-acid-induced hepatocyte death,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,,,"Useful for modeling liver-injury safety boundaries, cytokine/ROS axes, and protective pathway modulation.",ZHANG_TRIM16_YAP1_NRF2_SEPTIC_LIVER_INJURY_2026,septic_liver_injury_original_article,TRIM16 mediates YAP1 K63-linked ubiquitination to alleviate sepsis-induced acute liver injury through YAP/Nrf2 axis in mice,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,,,"Useful for modeling delivery-system differences, intracellular trafficking, and tissue/cell targeting assumptions.",ZHOU_TDEV_MEMBRANE_LEV_SIRNA_HCC_DELIVERY_2022,advanced_siRNA_delivery_original_article,Tumour-derived extracellular vesicle membrane hybrid lipid nanovesicles enhance siRNA delivery by tumour-homing and intracellular freeway transportation,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; not encoded in row-level synthetic tables,,,Deferred from row-level generation to avoid diluting therapeutic oligo toxicity focus.,KLEIN_NFI_CYP_HUMAN_LIVER_PHARMACOMETABOLISM_2025,human_liver_pharmacometabolism_original_article,Transcription factors of the Nuclear Factor I family control hepatocyte differentiation and cytochrome P450 activity in human liver,deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; do not reproduce source figures/tables/text,,,Useful for modeling non-oligo liver-injury stress axes and siRNA-validated rescue targets in copper-induced hepatotoxicity.,TANG_CUPROPTOSIS_WILSON_DISEASE_2025,copper_liver_injury_original_article,Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; generated variables only; do not reproduce source figures/tables/text,,,High-value modeling rigor source for PK/PD and preclinical-to-clinical translation of GalNAc-siRNAs.,SALIM_GALNAC_SIRNA_WB_PBPK_PD_2025,PBPK_PD_modeling_original_article,Whole-Body Physiologically Based Pharmacokinetic–Pharmacodynamic Modeling for Interspecies Translation and Mechanistic Characterization of Plasma and Tissue Disposition of GalNAc-siRNAs,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; not encoded in row-level synthetic tables,,,Deferred from row-level generation to keep source-specific generated rows focused on primary studies and modeling papers.,VAILLANT_HBV_OLIGONUCLEOTIDE_THERAPIES_REVIEW_2022,review_open_access,"Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects",deferred
,supports rigor/transparency by documenting why each source was used or deferred,CC BY; not encoded in row-level synthetic tables,,,"Potentially useful later for an optional notebook method, but deferred from the core generator to avoid diluting OligoTox focus.",LACALAMITA_PID_MICROARRAY_HIGH_ORDER_PATTERNS_2025,bioinformatics_methods_original_article,Unveiling complex patterns: An information-theoretic approach to high-order behaviors in microarray data,deferred
,supports rigor/transparency by documenting why each source was used or deferred,open access CC BY; generated variables only; do not reproduce source figures/tables/text,,,Final supplemental high-priority paper; encoded in off-target RISC mechanism table and used to refine seed/off-target hepatotoxicity logic.,AGARWAL_GALNAC_SIRNA_OFFTARGET_2025,mechanistic_original_article_open_access,Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates,include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,open access CC BY-NC; generated variables only; do not reproduce source figures/tables/text,,,"Used to anchor chemistry/delivery categories, approved landscape context, and data dictionary terminology.",EGLI_MANOHARAN_APPROVED_OLIGO_CHEMISTRY_2023,critical_review_open_access,"Chemistry, Structure and Function of Approved Oligonucleotide Therapeutics",include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,open access CC BY-NC-ND; generated variables only; do not reproduce source figures/tables/text,,,Adds original PNPLA3 ASO clinical target-engagement evidence beyond the PNPLA3 review already represented.,ARMISEN_AZD2693_PNPLA3_ASO_MASH_2025,phase1_clinical_and_preclinical_original_article_open_access,"AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: Two randomized phase I trials",include_full_or_direct_module
,supports rigor/transparency by documenting why each source was used or deferred,freely downloadable PDF; generated variables only; do not reproduce source figures/tables/text,,,Used to encode broad platform distinctions between single-stranded ASOs and double-stranded siRNAs.,CROOKE_RNA_TARGETED_THERAPEUTICS_2018,perspective_article,RNA-Targeted Therapeutics,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open access; generated variables only; do not reproduce source figures/tables/text,,,"Used to justify model_system, sequence_alignment, humanized_model, and surrogate_NAT metadata.",OLIVER_HILL_MODEL_SELECTION_NAT_2026,review_open_access,Model Selection in Preclinical Nucleic Acid Therapeutics Research,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,open access CC BY; generated variables only; do not reproduce source figures/tables/text,,,Used for current approved oligonucleotide landscape and GalNAc trend context.,ALSHAER_FDA_TIDES_HARVEST_2025,review_open_access,2025 FDA TIDES (Peptides and Oligonucleotides) Harvest,include_supporting_module_or_context
,supports rigor/transparency by documenting why each source was used or deferred,freely downloadable PDF; generated variables only; do not reproduce source figures/tables/text,,,Used to anchor HSD17B13 target rationale and protective liver phenotype variables.,ABULHUSN_HSD17B13_PROTECTIVE_VARIANT_2018,human_genetics_original_article,A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease,include_context_metadata
,supports rigor/transparency by documenting why each source was used or deferred,open access CC BY; generated variables only; do not reproduce source figures/tables/text,,,Used to distinguish target knockdown and steatosis effects from lack of fibrosis improvement in a specific mouse model.,MA_HSD17B13_ASO_FIBROSIS_MOUSE_2024,preclinical_original_article_open_access,Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model,include_context_metadata
defer,,,no,low_to_moderate_context_only,"Original liver/hepatocyte antiviral paper, but the therapeutic is small-molecule apilimod; siRNA is mechanistic validation rather than therapeutic oligo data.",RING_PIKFYVE_APILIMOD_HEV_ENTRY_2026,,,
defer,,,no,low_context_only,Systematic review and cardiac-focused; useful for background on RNAi safety but not row-level OligoTox generation.,SADDIQUE_RNAI_CARDIAC_FAILURE_SYSTEMATIC_REVIEW_2024,,,
add_supporting,,,rpsap52_lna_gapmer_ovarian_pdox.csv,moderate_supporting_ASO_modality_safety,Primary LNA GapmeR antisense therapeutic paper with in vitro and PDOX tumor-growth effects and no evident toxicity context.,RAMESH_KUMAR_RPSAP52_LNA_GAPMER_OVARIAN_PDOX_2025,,,
add_supporting,,,biologics_hyb_targeted_rna_delivery.csv,moderate_to_high_delivery_rigor,"Primary biologics-based RNA delivery paper adding EMNV/liposome hybrid siRNA loading, targeting, intracellular delivery, and liver-targeted siRNA delivery context.",KOSTYUSHEVA_BIOLOGICS_HYB_TARGETED_RNA_DELIVERY_2025,,,
defer,,,no,moderate_background_only,"Useful clinical GalNAc-ASO background, but review-only; reserve for final narrative rather than generated row-level table.",BHATIA_PELACARSEN_LPA_ASO_REVIEW_2025,,,