control_id,control_type,control_role,expected_behavior,control_rationale,source_basis,provenance_label,record_origin,license_for_generated_output,expected_direction,rationale,source_id,description,expected_response,expected_outcome CTRL_NEG_VEHICLE_MOCK,negative_control_vehicle_mock,baseline_no_active_oligo,no oligo-driven hepatotoxicity signal,Represents mock/vehicle exposure with dose set to zero.,OligoTox alignment memo control logic,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_LOW_RISK_OLIGO,negative_control_low_risk_oligo,low_sequence_chemistry_exposure_risk,"high viability, low ALT/AST proxy, low stress scores","Low PS content, low off-target burden, moderate GC content, low dose.",OligoTox predictor framework,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_CLINICAL_LOW_HEPATOTOX_RAPIROSIRAN,clinical_low_hepatotoxicity_reference,GalNAc_siRNA_clinical_safety_reference,low-to-moderate synthetic hepatotoxicity risk and stable liver injury readouts,Inspired by a Phase I GalNAc-siRNA trial reporting no evidence of drug-induced liver injury.,RAPIROSIRAN_SANYAL_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_HUMAN_LIVER_SPHEROID_TOLERATED,human_in_vitro_tolerated_reference,human_liver_spheroid_low_toxicity_context,sustained viability and low stress despite GalNAc-siRNA exposure,Inspired by long-term human liver spheroid GalNAc-siRNA screening with no observed hepatotoxicity under conditions used.,LIVER_SPHEROID_SCHOLTEN_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_HIGH_PS_HIGH_DOSE,positive_control_high_PS_high_dose,chemistry_exposure_high_risk,reduced viability and elevated stress/liver injury proxy,High phosphorothioate content and high dose represent a stress-test positive control.,OligoTox alignment memo predictor families,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_HIGH_OFFTARGET,positive_control_high_offtarget,sequence_offtarget_high_risk,transcriptomic perturbation and stress response signal,High predicted off-target burden and long complementarity segments stress-test sequence-dependent toxicity.,OligoTox alignment memo sequence predictor families,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_TRANSCRIPTOMIC_STRESS,positive_control_transcriptomic_stress,pathway_stress_high_risk,"elevated transcriptomic perturbation, apoptosis, and stress response scores",Designed to represent oligo-induced pathway stress for model benchmarking.,OligoTox alignment memo readout logic,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_LNA_GAPMER_HIGH_RISK,positive_control_LNA_gapmer_high_risk,gapmer_chemistry_high_risk,higher synthetic risk due to gapmer/LNA/high-PS configuration,Represents sequence/chemistry-dependent gapmer risk used as a positive control pattern.,OligoTox Phase 1 ideation logic and alignment memo,literature_grounded_generated,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_TARGETED_LNP_ASGPR_SAFE_WINDOW,negative_control_targeted_LNP_safe_window,delivery_low_risk_reference,high hepatic targeting score with low delivery-related stress,"Represents a small, neutral/slightly negative, PEGylated or ligand-targeted lipid nanocarrier within a liver-targeting size window.",MOHAMED_NANOPARTICLE_HEPATITIS_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_DELIVERY_RELATED_NP_STRESS,positive_control_delivery_related_nanocarrier_stress,delivery_high_risk_reference,"elevated delivery-related stress, immunogenicity, Kupffer clearance, and oxidative stress markers",Represents a high-risk delivery context such as cationic or inorganic nanoparticle exposure with larger particle size or oxidative-stress potential.,MOHAMED_NANOPARTICLE_HEPATITIS_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_BALANCED_HYBRID_RNA_LNP,negative_control_balanced_hybrid_RNA_LNP,balanced_payload_delivery_reference,balanced RNA co-delivery with strong payload function but without a direct hepatotoxicity-positive label,"Represents a fluorinated LNP-style dual RNA payload with siRNA:mRNA around 3:7 and high encapsulation efficiency, used as delivery/payload context rather than direct toxicity evidence.",MENG_HYBRID_RNA_LNP_HCC_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_IMMUNE_ACTIVATING_RNA_LNP_STRESS,positive_control_immune_activating_RNA_LNP_stress,immune_activation_stress_reference,"elevated immune-activation and inflammatory-stress context, with careful separation from direct oligo hepatotoxicity",Represents a strong RNA-LNP immune-activation context for stress-testing inflammatory readout generation.,MENG_HYBRID_RNA_LNP_HCC_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_APOB_ASO_LOW_LIPID_STRESS,negative_control_APOB_ASO_low_lipid_stress,lipid_homeostasis_low_stress_reference,modest APOB inhibition context with low lipid-export stress and preserved viability proxy,"Represents a low-dose Mipomersen-like APOB ASO context used as supporting lipid-homeostasis control, not as a direct hepatotoxicity claim.",CHEN_OVARIAN_MTTP_APOB_MIPOMERSEN_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_APOB_ASO_LIPID_EXPORT_STRESS,positive_control_APOB_ASO_lipid_export_stress,lipid_export_stress_reference,"high APOB inhibition, suppressed VLDL-apoB secretion proxy, and increased lipid-stress context",Represents high APOB-ASO inhibition under lipid/heat-stress style context for stress-testing lipid-homeostasis fields.,CHEN_OVARIAN_MTTP_APOB_MIPOMERSEN_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_SULT1B1_SIRNA_LIPID_RESCUE,negative_control_SULT1B1_siRNA_lipid_rescue,MASLD_epigenetic_lipid_rescue_reference,"lower SULT1B1 activity proxy, reduced lipid-accumulation context, and low-to-moderate hepatotoxicity score","Represents siRNA-mediated SULT1B1 knockdown in hepatocyte lipid-accumulation context as a rescue/low-risk benchmark, separated from direct oligo-toxicity claims.",LU_SULT1B1_SE_MASLD_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_MASLD_EPIGENETIC_LIPID_ACCUMULATION,positive_control_MASLD_epigenetic_lipid_accumulation,H3K27ac_CEBPB_SULT1B1_lipid_stress_reference,"high H3K27ac/CEBPB/SULT1B1 proxies, increased lipid accumulation, and elevated liver-stress context",Represents oleate/high-H3K27ac MASLD-like hepatocyte lipid accumulation for stress-testing liver-disease context fields.,LU_SULT1B1_SE_MASLD_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_ANGPTL3_SIRNA_LIVER_SAFETY,negative_control_ANGPTL3_siRNA_liver_safety,ARO_ANG3_like_liver_safety_reference,moderate-to-high ANGPTL3 inhibition with low transaminase signal and hepatic-fat reduction context,Represents an ARO-ANG3-like GalNAc-siRNA liver-safety context with no major liver signal and possible hepatic fat reduction.,OOSTVEEN_ANGPTL3_LIVER_SAFETY_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_ANGPTL3_ASO_HEPATIC_FAT_ALT_SIGNAL,positive_control_ANGPTL3_ASO_hepatic_fat_ALT_signal,vupanorsen_like_liver_safety_signal_reference,very high ANGPTL3 inhibition with increased hepatic-fat and ALT/AST signal context,Represents a vupanorsen-like high-dose GalNAc-ASO context where high target inhibition was associated with transaminase and hepatic-fat signals.,OOSTVEEN_ANGPTL3_LIVER_SAFETY_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_PNPLA3_I148M_HOMOZYGOUS_LIPID_STRESS,positive_control_PNPLA3_I148M_homozygous_lipid_stress,PNPLA3_genetic_liver_stress_reference,GG/I148M homozygous genotype with amplified lipid-droplet accumulation and MASLD-like liver-stress context,"Represents the high-risk PNPLA3 I148M homozygous context described in human genetics literature, especially under adiposity/metabolic stress.",PNPLA3_ROMEO_VALENTI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_PNPLA3_SIRNA_HOMOZYGOTE_RESCUE,negative_control_PNPLA3_siRNA_homozygote_rescue,PNPLA3_precision_therapy_rescue_reference,PNPLA3 I148M homozygous context with siRNA-like knockdown and reduced hepatic-fat/inflammation proxies,Represents genotype-targeted PNPLA3 silencing as a precision-therapy rescue benchmark for homozygous carriers.,PNPLA3_ROMEO_VALENTI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_PNPLA3_HETEROZYGOUS_UNCERTAIN_RESPONSE,context_control_PNPLA3_heterozygous_uncertain_response,PNPLA3_heterozygote_response_uncertainty_reference,heterozygous PNPLA3 context with uncertain or weaker response to PNPLA3 silencing,Represents the caution that PNPLA3 silencing may behave differently in heterozygotes because wild-type PNPLA3 activity may remain beneficial.,PNPLA3_ROMEO_VALENTI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_CHOLESTEROL_SIRNA_MUSCLE_TOLERATED,negative_control_cholesterol_siRNA_extrahepatic_delivery_tolerated,extrahepatic_delivery_tolerability_reference,skeletal muscle knockdown with low liver-marker signal proxy,"Represents systemic cholesterol-conjugated, chemically modified siRNA delivery with measurable skeletal-muscle and diaphragm knockdown and no strong liver/kidney marker worsening signal.",ENGELBEEN_ALK4_MUSCLE_SIRNA_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_EXTRAHEPATIC_SIRNA_LIVER_EXPOSURE,context_control_extrahepatic_siRNA_with_liver_exposure,distribution_context_reference,extrahepatic muscle delivery plus measurable liver exposure/knockdown without being labeled as a hepatotoxicity-positive control,Represents the fact that lipid-conjugated systemic siRNAs can affect non-liver target tissues while still showing liver exposure; useful for separating delivery distribution from liver injury.,ENGELBEEN_ALK4_MUSCLE_SIRNA_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_PERSONALIZED_ASO_ACCEPTABLE_SAFETY_PROFILE,negative_control_patient_customized_splice_ASO_acceptable_safety,ASO_platform_safety_workflow_reference,splice-modulating ASO workflow with low direct hepatotoxicity signal and explicit monitoring/toxicology context,"Represents a customized 2prime-MOE phosphorothioate ASO workflow with off-target screening, preclinical toxicology, intrathecal dosing, and no serious adverse events reported in the N-of-1 context; used only as safety-workflow context, not liver-efficacy evidence.",KIM_MILASEN_CUSTOM_ASO_2019,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_CUSTOM_ASO_TOX_WORKFLOW,context_control_custom_ASO_design_and_toxicology_workflow,translational_workflow_reference,"patient-specific ASO design, fibroblast validation, animal toxicology, dose escalation, and clinical monitoring are represented as workflow variables rather than hepatotoxicity positives","Represents the translational pipeline from genomic diagnosis and splice-defect identification to ASO design, in vitro validation, toxicology, dosing, PK, and monitoring.",KIM_MILASEN_CUSTOM_ASO_2019,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_GALNAC_ASO_NAFLD_TARGETED_LIVER_SAFE_WINDOW,negative_control_GalNAc_ASO_metabolic_liver_targeted_safe_window,hepatocyte_targeted_ASO_metabolic_benefit_reference,"metabolic-target benefit with low generated ALT/AST/GGT, low IFN response, and low kidney-injury proxy",Represents a GalNAc-conjugated ASO context with improved hepatocyte targeting and specificity for metabolic liver disease targets.,KEATING_ASO_OBESITY_NAFLD_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_HIGH_AFFINITY_GAPMER_HEPATOTOX_SEQUENCE_MOTIF,positive_control_high_affinity_gapmer_sequence_motif_hepatotoxicity,ASO_sequence_chemistry_hepatic_injury_reference,"higher hepatic-injury, off-target, RNase-H1 promiscuity, and ALT/AST/GGT proxies","Represents known ASO-development cautions: high-affinity gapmer chemistry, sequence-motif toxicity, and liver enzyme monitoring signals.",KEATING_ASO_OBESITY_NAFLD_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ASO_TYPE_I_IFN_OFFTARGET,context_control_ASO_type_I_interferon_offtarget_response,immune_offtarget_response_reference,type-I-interferon/off-target response context separated from direct hepatocyte cytotoxicity,"Represents ASO off-target immune-response context described for some ASO sequences and tissues, useful for distinguishing liver injury from immune confounding.",KEATING_ASO_OBESITY_NAFLD_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_LNA_GAPMER_SEQUENCE_REDESIGN_LOW_TOX,negative_control_LNA_gapmer_sequence_redesign_low_toxicity,sequence_modification_low_risk_redesign_reference,low generated ALT/AST proxy despite LNA/PS gapmer context because sequence-motif risk is reduced,Represents the concept that small sequence/redesign changes can lower hepatotoxic potential while preserving an oligo design family.,HAGEDORN_LNA_HEPATOTOX_RF_2013,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_LNA_GAPMER_SEQUENCE_PATTERN_HIGH_TOX,positive_control_LNA_gapmer_sequence_pattern_high_toxicity,sequence_modification_high_risk_reference,high generated ALT/AST proxy and high sequence-modification hepatotoxicity probability,Represents LNA-modified phosphorothioate gapmer designs whose sequence and modification pattern predict high hepatotoxic potential.,HAGEDORN_LNA_HEPATOTOX_RF_2013,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_DISTANCE_LIMITED_SEQUENCE_TOX_PREDICTION,context_control_sequence_toxicity_prediction_distance_limit,model_applicability_domain_reference,prediction confidence is reduced when sequence/edit-distance context is far from the training-like region,Represents the applicability-domain concept that sequence-toxicity prediction is stronger near training-like oligo designs and weaker farther away.,HAGEDORN_LNA_HEPATOTOX_RF_2013,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_HSD17B13_RAPIROSIRAN_NO_DILI_PD,negative_control_clinical_GalNAc_siRNA_no_DILI_PD_response,HSD17B13_GalNAc_siRNA_clinical_PD_safety_reference,robust HSD17B13 mRNA knockdown with no generated drug-induced liver injury signal and numerically lower ALT/AST context,Represents rapirosiran-like GalNAc-siRNA clinical low-hepatotoxicity reference for MASH with liver target knockdown.,RAPIROSIRAN_SANYAL_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_HSD17B13_HEPATITIS_E_CONFOUNDED_ALT_AST,context_control_non_drug_transaminase_confounding,separate_drug_signal_from_intercurrent_hepatitis_event,ALT/AST event is labeled as confounded/non-treatment-related rather than assigned to oligo hepatotoxicity,Represents the need to distinguish oligo-driven DILI from intercurrent liver infections or unrelated clinical events.,RAPIROSIRAN_SANYAL_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_HSD17B13_PLACEBO_MASH_ALT_AST_REFERENCE,context_control_MASH_placebo_liver_enzyme_reference,background_MASH_ALT_AST_variability_reference,background ALT/AST and NAS variability without active HSD17B13 knockdown,Represents MASH disease-background variability and placebo comparator context for interpreting generated clinical liver readouts.,RAPIROSIRAN_SANYAL_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_VIR2218_ESCPLUS_LOW_ALT,negative_control_ESCplus_GalNAc_siRNA_low_ALT,seed_region_modified_siRNA_hepatic_safety_reference,"low ALT proxy, reduced seed-mediated off-target proxy, retained on-target activity context",Represents VIR-2218-like ESC+ GalNAc-siRNA context with glycol nucleic acid seed-region modification and lower ALT elevation signal relative to the parent ALN-HBV context.,GANE_VIR2218_ALNHBV_HBV_RNAI_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_ALNHBV_SEED_OFFTARGET_ALT,positive_control_parent_ESC_siRNA_seed_offtarget_ALT,parent_siRNA_ALT_elevation_reference,higher seed-mediated off-target proxy and higher ALT elevation proxy,Represents ALN-HBV parent molecule context where ALT elevations were more pronounced than with VIR-2218 in mouse and healthy-volunteer comparisons.,GANE_VIR2218_ALNHBV_HBV_RNAI_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_VIR2218_CHBV_HBSAG_REDUCTION,context_control_clinical_antiviral_PD_not_hepatotoxicity_positive,HBsAg_reduction_and_PD_durability_reference,dose-dependent HBsAg reduction with generally encouraging hepatic safety context,"Represents two-dose VIR-2218 clinical cHBV context: HBsAg reduction, prolonged pharmacodynamic effect, and ALT monitoring separated from direct DILI labeling.",GANE_VIR2218_ALNHBV_HBV_RNAI_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_ZILEBESIRAN_GALNAC_AGT_PLATFORM_LOW_HEPATIC_INJURY,negative_platform_context_control,GalNAc-siRNA hepatic AGT knockdown with long-duration PD and no direct hepatotoxicity signal encoded,,,DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,,dbbun_generated,CC BY 4.0,low_hepatotoxicity_context,"Represents zilebesiran-like hepatocyte-targeted AGT siRNA as a low direct-hepatotoxicity platform context, while tracking systemic RAAS safety separately.",,,, CTRL_CONTEXT_ZILEBESIRAN_RAAS_HYPERKALEMIA_RENAL_MONITORING,systemic_safety_context_control,"RAAS-suppression safety-monitoring context including hyperkalemia, hypotension, and renal-function changes",,,DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,,dbbun_generated,CC BY 4.0,systemic_monitoring_not_primary_hepatotoxicity,"Keeps hyperkalemia, hypotension, and eGFR/creatinine monitoring separate from hepatotoxicity so the dataset does not confuse systemic pharmacology with liver injury.",,,, CTRL_CONTEXT_ZILEBESIRAN_LONG_PD_ENDOSOMAL_DEPOT,pharmacodynamic_durability_context_control,long-duration GalNAc-siRNA hepatocyte endosomal-depot and RISC-recycling context,,,DUDZICZ_ZILEBESIRAN_HTN_REVIEW_2025,,dbbun_generated,CC BY 4.0,durable_PD_context,"Represents prolonged siRNA effect from hepatocyte uptake, endosomal storage, and RISC-mediated target mRNA degradation.",,,, CTRL_NEG_TTR_GALNAC_SIRNA_BULGE14_ACTIVE_LOW_TOX,negative_or_low_toxicity_mechanistic_control,GalNAc-siRNA with tolerated position-14 guide-strand bulge and preserved target repression,,"Represents a tolerated guide-strand bulge context with receptor-mediated GalNAc uptake and target repression, without adding direct hepatotoxicity signal.",HAUPTMANN_SIRNA_BULGES_GALNAC_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,low_hepatotoxicity_with_preserved_on_target_activity,,,,, CTRL_POS_TERMINAL_BULGE_OFFTARGET_REPRESSION_RISK,positive_offtarget_risk_control,Degenerate target-site / terminal guide-strand bulge off-target repression risk,,Represents the finding that short bulges or nucleotide omissions near guide termini can still support reporter repression and therefore should be tracked as off-target prediction risk.,HAUPTMANN_SIRNA_BULGES_GALNAC_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,higher_offtarget_prediction_risk_without_direct_hepatotoxicity_claim,,,,, CTRL_CONTEXT_SEED_REGION_BULGE_ACTIVITY_LOSS,context_activity_loss_control,Seed-region guide-strand bulge context with reduced siRNA activity,,"Represents reduced activity when guide-strand bulges are positioned in seed-region contexts, useful for distinguishing loss of efficacy from toxicity.",HAUPTMANN_SIRNA_BULGES_GALNAC_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,lower_on_target_activity_context,,,,, CTRL_CONTEXT_FBLL1_HIGH_HCC_MALIGNANT_STATE,context_liver_cancer_malignant_state_control,High-FBLL1 malignant hepatocyte / HCC tumor-niche context,,"Represents FBLL1 enrichment in malignant hepatocytes and tumor regions, useful for liver-disease context annotation without treating this as direct oligonucleotide hepatotoxicity.",XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,higher_HCC_malignant_context_not_direct_oligotox_signal,,,,, CTRL_NEG_FBLL1_SIRNA_KNOCKDOWN_HCC_GROWTH_SUPPRESSION,negative_growth_context_control,siRNA-mediated FBLL1 knockdown suppresses HCC proliferation and colony formation,,"Represents FBLL1-targeting research siRNA as a functional knockdown context that decreases HCC growth phenotypes, separating RNAi functional effect from hepatotoxicity.",XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,lower_HCC_growth_context_with_research_siRNA_knockdown,,,,, CTRL_CONTEXT_FBLL1_CMYC_EGFR_MAPK_ACTIVATION,context_oncogenic_signaling_control,FBLL1-associated c-Myc / EGFR ligand / MAPK activation context,,"Represents transcriptional and protein-level oncogenic signaling context linked to FBLL1 overexpression, including c-Myc, EGFR ligands, p-EGFR and p-ERK.",XIE_FBLL1_HCC_SPATIAL_MULTIOMICS_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,higher_oncogenic_signaling_context_not_direct_hepatotoxicity,,,,, CTRL_NEG_GALNAC_LNP_SIMKK4_BIOCOMPATIBLE_LOW_HEMOLYSIS,negative_delivery_biocompatibility_control,GalNAc-LNP-siMKK4 biocompatible hepatocyte-targeted delivery context,,"Represents the reported low hemolysis, low in vitro cytotoxicity, stable GalNAc-LNP-siMKK4 formulation, and hepatocyte-targeted uptake context rather than an oligo hepatotoxicity signal.",ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,low_direct_hepatotoxicity_delivery_biocompatible_context,,,,, CTRL_CONTEXT_GALNAC_LNP_SIMKK4_ACLF_REGENERATION,context_liver_regeneration_rescue_control,GalNAc-LNP-siMKK4 promotes liver regeneration in CCl4/partial-hepatectomy ACLF model,,"Represents MKK4 knockdown, reduced p38/apoptosis signaling, increased MKK7-JNK/ATF2/ELK1 proliferative signaling, hepatocyte proliferation, and liver function recovery context.",ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,regeneration_rescue_and_liver_function_recovery_context,,,,, CTRL_POS_CCL4_PHX_ACLF_INJURY_CONTEXT,positive_liver_injury_model_context_control,CCl4 plus partial-hepatectomy acute-on-chronic liver failure injury context,,"Represents the injured liver model background used to evaluate regeneration rescue; this is a high liver-injury context control, not evidence that the oligonucleotide delivery system itself is hepatotoxic.",ZHAI_GALNAC_LNP_SIMKK4_LIVER_REGEN_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,high_background_liver_injury_low_regeneration_without_effective_siMKK4,,,,, CTRL_POS_OGT_SEV_LSEC_CAPILLARIZATION_MASLD,positive_context_lipotoxic_hepatocyte_sEV,MASLD_LSEC_capillarization_and_ALT_AST_stress_context,"high OGT/O-GlcNAc/HNF1a-Ang2 signaling with LSEC defenestration, higher ALT/AST context, and MASLD progression proxy",Represents lipotoxic hepatocyte-derived sEV carrying OGT and promoting LSEC capillarization through HNF1a O-GlcNAcylation and Ang-2 activation.,WANG_OGT_SEV_LSEC_MASLD_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_OGT_KNOCKDOWN_SEV_REDUCED_CAPILLARIZATION,negative_mechanistic_context_OGT_depleted_sEV,reduced_OGT_sEV_cargo_and_reduced_LSEC_capillarization,lower OGT/O-GlcNAc/Ang-2 context and reduced capillarization relative to OGT-high sEV context,"Represents OGT knockdown in lipotoxic hepatocyte-derived sEV attenuating Ang-2 induction, sinusoidal defenestration, and MASLD worsening.",WANG_OGT_SEV_LSEC_MASLD_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_BAGN_OGLCNAC_INHIBITOR_MASLD_RESCUE,therapeutic_context_OGlcNAc_inhibitor_rescue,BAGN_reduces_HNF1a_OGlcNAcylation_Ang2_LSEC_capillarization_and_MASLD_progression,"dose-dependent reduction in O-GlcNAcylation, Ang-2, LSEC capillarization, ALT/AST, TG, inflammation, lipid deposition, collagen deposition, and alpha-SMA context",Represents BAGN inhibition of O-GlcNAcylation as a rescue context in HFD-induced MASLD mice.,WANG_OGT_SEV_LSEC_MASLD_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_HBX_MALAT1_IGF2BP3_HCC_ONCOGENIC_STATE,positive_context_control,HBx_MALAT1_m6A_IGF2BP3_oncogenic_HCC_state,,,DU_MALAT1_HBV_HCC_ASO_2025,,dbbun_generated,CC BY 4.0,higher_HCC_context_signal,"Models the high-risk HBV/HBx-related HCC context in which MALAT1 is upregulated, m6A-modified, stabilized/exported by IGF2BP3, and associated with proliferation, invasion, EMT, and poor prognosis.",,,, CTRL_NEG_ASO_MALAT1_HBV_HCC_TUMOR_SUPPRESSION,negative_or_rescue_control,ASO_MALAT1_suppression_of_HBV_related_HCC_progression,,,DU_MALAT1_HBV_HCC_ASO_2025,,dbbun_generated,CC BY 4.0,lower_HCC_context_signal_after_ASO_MALAT1,Models the ASO-MALAT1 rescue/intervention context where MALAT1 targeting suppresses xenograft and orthotopic HBV-related HCC progression and reduces EMT/intrahepatic spread signals.,,,, CTRL_CONTEXT_MALAT1_M6A_IGF2BP3_SHUTTLING,mechanistic_context_control,m6A_site_dependent_MALAT1_IGF2BP3_binding_and_cytoplasmic_export,,,DU_MALAT1_HBV_HCC_ASO_2025,,dbbun_generated,CC BY 4.0,mechanistic_context_not_direct_toxicity,"Captures the mechanism that METTL3/METTL14/WTAP-mediated m6A at MALAT1 sites 6021A and 7265A supports IGF2BP3 binding, MALAT1 stabilization, and nuclear-cytoplasmic shuttling.",,,, CTRL_POS_CD133_CSC_MASLD_HCC_MKI_RESISTANCE,positive_context_control,CD133_positive_CSC_MASLD_HCC_multikinase_inhibitor_resistance_state,,,PAN_CD133_MASLD_HCC_SIRNA_2025,,dbbun_generated,CC BY 4.0,higher_stemness_resistance_and_tumor_context_signal,"Models the high-risk MASLD-HCC context in which CD133-positive cancer stem cells show self-renewal, tumor-initiating capacity, Wnt/beta-catenin activation, and resistance to multikinase inhibitors.",,,, CTRL_NEG_VNP_SICD133_MKI_TUMOR_SUPPRESSION,negative_or_rescue_control,VNP_siCD133_plus_sorafenib_or_lenvatinib_tumor_suppression,,,PAN_CD133_MASLD_HCC_SIRNA_2025,,dbbun_generated,CC BY 4.0,lower_tumor_context_signal_after_siCD133_combination_therapy,"Models the therapeutic rescue context where nanoparticle-delivered CD133 siRNA sensitizes MASLD-HCC to sorafenib or lenvatinib and reduces tumor burden, Ki67, and Wnt/beta-catenin signaling.",,,, CTRL_CONTEXT_CD133_MYH9_BCATENIN_STEMNESS,mechanistic_context_control,CD133_MYH9_active_beta_catenin_stemness_axis,,,PAN_CD133_MASLD_HCC_SIRNA_2025,,dbbun_generated,CC BY 4.0,mechanistic_context_not_direct_toxicity,Captures the mechanism where CD133 interacts with MYH9 to stabilize active beta-catenin and propagate Wnt/beta-catenin signaling in MASLD-HCC cancer stem cells.,,,, CTRL_NEG_GALNAC_RBC_EV_HEPATOCYTE_TARGETED_SAFE,negative_delivery_safety_control,ctrl_neg_galnac_rbc_ev_hepatocyte_targeted_safe,,,HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,,dbbun_generated,CC BY 4.0,high_hepatocyte_targeting_low_direct_delivery_toxicity,GalNAc-modified RBC-EV ASGPR hepatocyte targeting with low systemic toxicity context.,,,, CTRL_NEG_RBC_EV_GALNAC_MIR155_ASO_ALF_RESCUE,negative_or_rescue_control,ctrl_neg_rbc_ev_galnac_mir155_aso_alf_rescue,,,HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,,dbbun_generated,CC BY 4.0,lower_ALF_liver_injury_and_cell_death_signal,"RBC-EV/GalNAc-miR-155-ASO rescue in acute liver injury with lower ALT/AST, inflammation, and PANoptosis context.",,,, CTRL_CONTEXT_GALNAC_RBC_EV_PJ34_NAFLD_RESCUE,therapeutic_context_control,ctrl_context_galnac_rbc_ev_pj34_nafld_rescue,,,HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,,dbbun_generated,CC BY 4.0,lower_steatosis_PAR_and_liver_injury_signal,GalNAc-RBC-EVs/PJ34 PARP-1/PAR reduction and NAFLD steatosis rescue context.,,,, CTRL_CONTEXT_GALNAC_RBC_EV_RAB7_SIRNA_PJ34_HCC,combination_delivery_context_control,ctrl_context_galnac_rbc_ev_rab7_sirna_pj34_hcc,,,HUANG_GALNAC_RBC_EV_LIVER_DISEASE_2025,,dbbun_generated,CC BY 4.0,higher_drug_retention_and_HCC_tumor_suppression_context,RBC-EV/GalNAc-Rab7-siRNA/PJ34 HCC co-delivery with drug-retention and tumor-suppression context.,,,, CTRL_CONTEXT_MELD_PLUS_HIGH_RISK_CIRRHOSIS,clinical_high_risk_context_control,ctrl_context_meld_plus_high_risk_cirrhosis,,,KARTOUN_MELD_PLUS_CIRRHOSIS_2017,,dbbun_generated,CC BY 4.0,higher_clinical_liver_severity_and_mortality_risk_context,"High MELD-Plus-like cirrhosis risk state with low albumin, high bilirubin/INR/creatinine/WBC, hyponatremia, longer admission, and high predicted post-discharge mortality.",,,, CTRL_NEG_MELD_PLUS_LOW_RISK_CIRRHOSIS,clinical_low_risk_context_control,ctrl_neg_meld_plus_low_risk_cirrhosis,,,KARTOUN_MELD_PLUS_CIRRHOSIS_2017,,dbbun_generated,CC BY 4.0,lower_clinical_liver_severity_context,Lower MELD-Plus-like cirrhosis risk state with more favorable structured laboratory profile and lower predicted post-discharge mortality.,,,, CTRL_CONTEXT_MELD_PLUS_EMR_VARIABLES,clinical_prediction_schema_context_control,ctrl_context_meld_plus_emr_variables,,,KARTOUN_MELD_PLUS_CIRRHOSIS_2017,,dbbun_generated,CC BY 4.0,schema_context_for_clinical_liver_outcome_prediction,"MELD-Plus variable-set context: MELD-Na components plus albumin, total cholesterol, WBC, age, and length of stay.",,,, CTRL_POS_ALD_ACETALDEHYDE_ROS_MITOCHONDRIAL_STRESS,positive_liver_stress_context,,,,,,dbbun_generated,CC BY 4.0,high_oxidative_liver_stress,,MA_FORMONONETIN_ALDH2_ALD_2025,"Alcohol-related liver injury context with acetaldehyde accumulation, ROS, lipid peroxidation, mitochondrial dysfunction, ALT/AST elevation, and fibrosis/liver-injury features.",, CTRL_NEG_FORMONONETIN_ALDH2_NRF2_HEPATOPROTECTION,negative_hepatoprotective_context,,,,,,dbbun_generated,CC BY 4.0,reduced_aldehyde_oxidative_liver_stress,,MA_FORMONONETIN_ALDH2_ALD_2025,"Formononetin-like rescue context with ALDH2 activation, lower acetaldehyde/4-HNE/TBARS, restored GSH/GPX4/NAD/ATP, and improved mitochondrial/liver-injury measures.",, CTRL_CONTEXT_ALDH2_NRF2_SIRNA_LOSS_OF_RESCUE,mechanistic_loss_of_rescue_context,,,,,,dbbun_generated,CC BY 4.0,mechanistic_dependency_context,,MA_FORMONONETIN_ALDH2_ALD_2025,AAV8 siRNA knockdown context in which loss of ALDH2 or Nrf2 reduces the formononetin-like rescue signal.,, CTRL_NEG_HNP_SIHOXB7_LOW_HEPATIC_SIGNAL,negative_systemic_siRNA_nanoparticle_safety_context,,,,,,dbbun_generated,CC BY 4.0,low_direct_hepatotoxicity_signal,,VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,Calcium phosphate hybrid nanoparticle siRNA context with low hemolysis and ALT/AST values remaining in a standard/non-injury range in treated animals.,, CTRL_CONTEXT_HOXB7_SIRNA_TAMOXIFEN_COTREATMENT,therapeutic_combination_context,,,,,,dbbun_generated,CC BY 4.0,combination_efficacy_context,,VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,"HOXB7 siRNA plus tamoxifen cotreatment context with tumor growth control, improved survival in advanced tumor animals, and systemic safety monitoring.",, CTRL_CONTEXT_HNP_CALCIUM_PHOSPHATE_ENDOSOMAL_ESCAPE,delivery_design_context,,,,,,dbbun_generated,CC BY 4.0,delivery_mechanism_context,,VALLE_HOXB7_HNP_TAMOXIFEN_BREAST_2024,"Calcium phosphate/PEG-pGlu nanoparticle design context with nanoscale size, siRNA encapsulation, acid-pH destabilization, and endosomal escape rationale.",, CTRL_NEG_PMEVL_SEV_SIPCSK9_LOW_SYSTEMIC_TOX,negative_sEV_siRNA_hepatic_delivery_safety_context,,,,,,dbbun_generated,CC BY 4.0,low_systemic_toxicity_with_hepatic_RNAi_activity,,WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,"PMEVL-engineered sEVs loaded with Pcsk9 siRNA suppress hepatic Pcsk9, restore LDLR, reduce LDL-C/total cholesterol, and preserve normal ALT/AST and organ histology context.",, CTRL_CONTEXT_PMEVL_N_MYRISTOYLATION_RNA_LOADING,RNA_loading_mechanism_context,,,,,,dbbun_generated,CC BY 4.0,high_sEV_RNA_loading_efficiency,,WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,"N-myristoylation-dependent PMEVL loading context for chemically synthesized siRNA/miRNA, endogenous miRNA, pri-miR-30a-based siRNA, multiple siRNAs, and mRNA cargoes into sEVs.",, CTRL_CONTEXT_PMEVL_ERK_AMPK_ANXA2_ESCRT_MECHANISM,sEV_biogenesis_and_sorting_mechanism_context,,,,,,dbbun_generated,CC BY 4.0,mechanistic_sEV_biogenesis_and_RNA_sorting_context,,WANG_PMEVL_SEV_SMALL_RNA_PCSK9_2026,"PMEVL mechanism context involving ERK1/2 activation, AMPK-autophagy inhibition, ANXA2/AGO2-mediated RNA recruitment, and ALIX/TSG101 ESCRT-mediated cargo sorting.",, CTRL_CONTEXT_PRECLINICAL_OLIGO_SAFETY_FRAMEWORK,preclinical_safety_framework_context,,,,,,dbbun_generated,CC BY 4.0,framework_context_not_intrinsic_toxicity,,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,"General therapeutic-oligonucleotide safety framework separating sequence/hybridization-dependent on/off-target effects, sequence-independent Cmax effects, and sequence-dependent hybridization-independent liver/kidney/inflammatory toxicities.",, CTRL_POS_SEQUENCE_MOTIF_GAPMER_LIVER_RISK,positive_sequence_dependent_gapmer_hepatotoxicity_risk_context,,,,,,dbbun_generated,CC BY 4.0,higher_liver_toxicity_risk,,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,High-affinity PS gapmer sequence/modification patterns can show liver-toxicity risk independent of intended target knockdown or total liver concentration; sequence motifs and in vitro screens help remove risky candidates.,, CTRL_CONTEXT_HYBRIDIZATION_OFFTARGET_SCREENING,hybridization_dependent_offtarget_screening_context,,,,,,dbbun_generated,CC BY 4.0,offtarget_risk_assessment_context,,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,"Safety assessment should include transcriptome-wide in silico off-target screening, in vitro potency confirmation for candidate off-target transcripts, and consequence assessment when margins are insufficient.",, CTRL_CONTEXT_GALNAC_PRODUCTIVE_UPTAKE_HEPATOCYTE,GalNAc_productive_uptake_hepatocyte_context,,,,,,dbbun_generated,CC BY 4.0,improved_hepatocyte_productive_uptake_context,,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,"GalNAc conjugation improves hepatocyte productive uptake of ASOs and siRNAs through ASGR/ASGPR-mediated delivery, changing potency, dose, distribution, and safety-assessment context.",, CTRL_CONTEXT_CMAX_COMPLEMENT_COAGULATION_MONITORING,Cmax_dependent_complement_coagulation_context,,,,,,dbbun_generated,CC BY 4.0,Cmax_monitoring_context,,ANDERSSON_PRECLINICAL_OLIGO_SAFETY_2022,"Some PS-ASO effects, including coagulation-time prolongation and alternative complement activation, are plasma Cmax-related, transient, and should be modeled separately from sequence-specific hepatotoxicity.",, CTRL_POS_IFNA_DISULFIDPTOSIS_HCC,positive_cell_death_context,,,,,,dbbun_generated,CC BY 4.0,increased_disulfide_stress_and_cell_death,Provides a positive noncanonical liver-cell-death context that can help distinguish oxidative/disulfide stress from classic oligo sequence toxicity.,,"IFN-alpha-treated HepG2/Huh7-like positive context with disulfide-linked protein aggregation, NADPH depletion, and F-actin collapse.",, CTRL_NEG_DPEN_DISULFIDPTOSIS_RESCUE,negative_rescue_context,,,,,,dbbun_generated,CC BY 4.0,reduced_disulfide_stress,Provides a rescue/control row for disulfide-bond stress phenotypes.,,"D-penicillamine rescue context that partially reverses IFN-alpha-associated disulfide accumulation, NADPH depletion, and F-actin collapse.",, CTRL_CONTEXT_SLC7A11_KD_IFNA_AGGRAVATION,mechanistic_context,,,,,,dbbun_generated,CC BY 4.0,SLC7A11_not_sufficient_to_explain_IFN_alpha_disulfidptosis,Encodes the distinction between canonical SLC7A11-associated disulfidptosis and the paper's proposed SLC7A11-independent or partially independent mechanism.,,SLC7A11 siRNA knockdown context in which IFN-alpha-associated high-molecular-weight protein aggregation is aggravated rather than reduced.,, CTRL_CONTEXT_IFNA_ISG_B2M_USP18_PSME1,candidate_gene_context,,,,,,dbbun_generated,CC BY 4.0,candidate_interferon_stress_genes_upregulated,Adds candidate interferon-stimulated-gene context for liver cancer cell stress and disulfidptosis-associated phenotype modeling.,,"IFN-alpha candidate-gene context with B2M, USP18, and PSME1 upregulation, including PSME1 protein-level increase.",, CTRL_NEG_GALNAC_ESC_SIRNA_PLATFORM_LOW_TOX,negative_platform_safety_control,,,,,,dbbun_generated,CC BY 4.0,low_hepatotoxicity_with_platform_safety_monitoring,Represents the nonadverse platform-safety pattern for selected GalNAc-siRNAs in short-term rat/monkey toxicology.,,"ESC GalNAc-siRNA platform context with hepatocyte-targeted ASGPR uptake, limited PS content, 2prime-OMe/2prime-F chemistry, and low systemic toxicity at screened doses.",, CTRL_POS_GALNAC_SIRNA_SEED_OFFTARGET_RAT_HEPATOTOX,positive_sequence_offtarget_hepatotoxicity_control,,,,,,dbbun_generated,CC BY 4.0,increased_seed_offtarget_hepatotoxicity,Encodes the key GalNAc-siRNA safety-screening failure mode: seed-mediated off-target hepatotoxicity at supratherapeutic dose.,,GalNAc-siRNA seed-region off-target context associated with rat hepatocellular degeneration/coagulative necrosis and liver-enzyme elevation at exaggerated doses.,, CTRL_CONTEXT_GALNAC_SIRNA_LIVER_KIDNEY_RES_DISTRIBUTION,distribution_accumulation_context,,,,,,dbbun_generated,CC BY 4.0,organ_distribution_and_accumulation_monitoring,Adds the platform pattern of liver/kidney/RES findings rather than treating every histologic finding as direct adverse hepatotoxicity.,,"GalNAc-siRNA distribution context with pharmacodynamic liver exposure, kidney elimination, and reticuloendothelial-system histology findings that are often nonadverse and reversible.",, CTRL_CONTEXT_INCLISIRAN_FH_LDL_PWV_RESPONSE,clinical_PCSK9_response_context,,,,,,dbbun_generated,CC BY 4.0,PCSK9_knockdown_lipid_and_vascular_response,"Adds clinical GalNAc-siRNA response context for PCSK9 targeting, without treating lipid efficacy as hepatotoxicity.",,Inclisiran-treated familial-hypercholesterolemia context with LDL-C/ApoB/non-HDL-C/Lp(a) reductions and PWV improvement over six months.,, CTRL_NEG_INCLISIRAN_ALT_AST_STABLE_REALWORLD,negative_clinical_liver_enzyme_monitoring_control,,,,,,dbbun_generated,CC BY 4.0,stable_ALT_AST_CPK_monitoring,Provides clinical tolerability/liver-enzyme monitoring context for a GalNAc-siRNA PCSK9 therapeutic.,,Inclisiran real-world monitoring context where liver and muscle enzymes remain similar before and after treatment.,, CTRL_CONTEXT_GALNAC_ASGPR_LIVER_DELIVERY_REVIEW,delivery_platform_context,,,,,,dbbun_generated,CC BY 4.0,hepatocyte_targeted_productive_uptake_context,Encodes the core GalNAc delivery mechanism that explains why liver-targeted oligonucleotides can be dosed at lower levels than unconjugated or LNP-formulated alternatives.,,General GalNAc-ASGPR hepatocyte delivery context for liver-targeted ASO/siRNA therapeutics with rapid receptor-mediated uptake and intracellular endosomal processing.,, CTRL_CONTEXT_GALNAC_ASO_HEPATOCYTE_UPTAKE_POTENCY,ASO_hepatocyte_uptake_potency_context,,,,,,dbbun_generated,CC BY 4.0,increased_hepatocyte_uptake_and_lower_required_dose,Adds the review's ASO delivery message: GalNAc conjugation changes cellular liver distribution and can improve clinical potency by roughly an order of magnitude or more.,,GalNAc-ASO context where liver uptake shifts toward hepatocytes and potency improves relative to naked ASO for hepatocyte targets.,, CTRL_CONTEXT_GALNAC_SIRNA_ESCPLUS_SEED_SAFETY,siRNA_seed_region_safety_mitigation_context,,,,,,dbbun_generated,CC BY 4.0,reduced_seed_offtarget_hepatotoxicity_risk,Connects GalNAc-siRNA chemistry optimization to lower off-target toxicity risk and lower dose exposure.,,GalNAc-siRNA ESC/ESC+ chemistry context with seed-region off-target mitigation by destabilizing seed interactions while maintaining potency.,, CTRL_CONTEXT_GALNAC_REVERSIR_REVERSAL_SAFETY,reversal_safety_context,,,,,,dbbun_generated,CC BY 4.0,reversible_RISC_bound_siRNA_activity_context,Adds a safety-control concept for long-duration siRNA pharmacology: deliberate reversal of target silencing after GalNAc-siRNA dosing.,,Reversir-like GalNAc-conjugated oligonucleotide antidote concept for reversing siRNA silencing if toxicity is encountered.,, CTRL_CONTEXT_SIRNA_RISC_AGO2_MECHANISM,siRNA_mechanism_context,,,,,,dbbun_generated,CC BY 4.0,sequence_specific_RISC_mediated_target_knockdown,Encodes the mechanistic backbone needed to interpret therapeutic siRNA potency and off-target effects.,,"Canonical siRNA mechanism context: guide-strand loading into AGO2/RISC, passenger-strand removal, complementary mRNA cleavage, and reduced target-protein synthesis.",, CTRL_CONTEXT_SIRNA_PKPD_BARRIERS,siRNA_pharmacology_barrier_context,,,,,,dbbun_generated,CC BY 4.0,low_unmodified_siRNA_exposure_without_modification_or_delivery,"Adds baseline PK/PD barriers that justify GalNAc conjugation, LNP encapsulation, and chemical stabilization.",,"Naked siRNA pharmacology-barrier context: poor tissue penetration, endosomal escape limitation, nuclease degradation, rapid renal clearance, and need for stabilization/delivery systems.",, CTRL_CONTEXT_SIRNA_IMMUNE_OFFTARGET_SCREENING,immune_and_offtarget_safety_context,,,,,,dbbun_generated,CC BY 4.0,flag_for_offtarget_and_immunostimulatory_risk_assessment,Adds safety interpretation for distinguishing intended knockdown from off-target or immune-mediated toxicity.,,"siRNA safety-screening context for immune activation, TLR/cytokine responses, incomplete pairing, seed-region off-target silencing, and RISC/miRNA-pathway competition.",, CTRL_CONTEXT_APPROVED_GALNAC_SIRNA_CLINICAL_TRANSLATION,approved_clinical_siRNA_context,,,,,,dbbun_generated,CC BY 4.0,clinically_translated_liver_targeted_siRNA_platform_context,Connects generated OligoTox records to clinically validated liver-directed siRNA design and monitoring concepts.,,"Approved and clinical-stage siRNA landscape context including GalNAc-delivered givosiran, lumasiran, inclisiran, and other liver-targeted siRNA programs.",, CTRL_POS_LNA_GAPMER_HIGH_OTE_ALT_AST,positive_control,,,,,,dbbun_generated,CC BY 4.0,,,KAMOLA_ASO_HEPATOTOX_SCREEN_2017,High-risk LNA gapmer-like ASO control with many predicted/potent off-target effects and elevated ALT/AST/liver-weight signals.,high_hepatotoxicity, CTRL_NEG_LNA_GAPMER_SELECTIVE_LOW_HEPATOX,negative_control,,,,,,dbbun_generated,CC BY 4.0,,,KAMOLA_ASO_HEPATOTOX_SCREEN_2017,Cleaner/selective LNA gapmer-like ASO control with low predicted off-target burden and minimal ALT/AST signal.,low_hepatotoxicity, CTRL_CONTEXT_ACUTE_MOUSE_ASO_HEPATOX_SCREEN,assay_context_control,,,,,,dbbun_generated,CC BY 4.0,,,KAMOLA_ASO_HEPATOTOX_SCREEN_2017,Context control representing a streamlined acute mouse screen using plasma ALT/AST and liver-weight endpoints to rank ASO hepatotoxicity.,screening_context, CTRL_CONTEXT_TRANSCRIPTOME_WIDE_OTE_SELECTIVITY,computational_context_control,,,,,,dbbun_generated,CC BY 4.0,,,KAMOLA_ASO_HEPATOTOX_SCREEN_2017,Context control representing in silico OTE prediction plus transcriptome-wide selectivity confirmation as a mitigation strategy.,selectivity_context, CTRL_NEG_LNP_AGO1_ASO_ALT_AST_STABLE,negative_control,,,,,,dbbun_generated,CC BY 4.0,,,LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,LNP-delivered AGO1 LNA-gapmer ASO-like control with therapeutic knockdown context and no modeled ALT/AST hepatotoxicity signal.,low_hepatotoxicity_with_liver_function_monitoring, CTRL_CONTEXT_ENDOTHELIAL_AGO1_NFKB_INFLAMMATION,mechanism_context_control,,,,,,dbbun_generated,CC BY 4.0,,,LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,Context control representing endothelial nuclear AGO1 interaction with NF-kB/p65 and pro-inflammatory gene activation.,vascular_inflammation_context, CTRL_CONTEXT_LNP_ASO_HYPERLIPIDEMIA_LIVER_FUNCTION,disease_model_context_control,,,,,,dbbun_generated,CC BY 4.0,,,LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,"Context control representing AAV9-PCSK9/high-fat-high-cholesterol stress with lipid profile, liver function, steatosis, fibrosis, and atherosclerosis endpoints.",metabolic_liver_vascular_context, CTRL_CONTEXT_EC_HEPATOCYTE_PARACRINE_METABOLISM,cell_interaction_context_control,,,,,,dbbun_generated,CC BY 4.0,,,LIU_ENDOTHELIAL_AGO1_LNP_ASO_2025,Context control representing endothelial-hepatocyte paracrine signaling affecting inflammatory and lipid-metabolism gene programs.,paracrine_liver_metabolism_context, CTRL_NEG_GYS1_ASO_NO_ALT_AST_ELEVATION,negative_control_systemic_ASO_tolerability,,,,,,dbbun_generated,CC BY 4.0,,,WEISS_GYS1_ASO_POMPE_PREPRINT_2024,Systemically administered GYS1 PS-cEt gapmer ASO context with no modeled ALT/AST elevation signal and no major organ-weight toxicity signal.,low_hepatotoxicity_with_systemic_tolerability_monitoring, CTRL_CONTEXT_GYS1_ASO_SUBSTRATE_REDUCTION_POMPE,therapeutic_mechanism_context_control,,,,,,dbbun_generated,CC BY 4.0,,,WEISS_GYS1_ASO_POMPE_PREPRINT_2024,Context control representing Gys1 RNase-H1 gapmer ASO substrate-reduction therapy reducing glycogen accumulation in Pompe muscle.,target_knockdown_and_substrate_reduction_context, CTRL_CONTEXT_GYS1_ASO_ERT_COMBINATION,combination_therapy_context_control,,,,,,dbbun_generated,CC BY 4.0,,,WEISS_GYS1_ASO_POMPE_PREPRINT_2024,"Context control representing GYS1 ASO plus recombinant GAA enzyme replacement therapy, combining reduced new glycogen synthesis with enhanced clearance.",combination_therapy_translatability_context, CTRL_CONTEXT_GYS1_GYS2_ISOFORM_SPECIFICITY,specificity_context_control,,,,,,dbbun_generated,CC BY 4.0,,,WEISS_GYS1_ASO_POMPE_PREPRINT_2024,Context control representing isoform-specific ASO design challenge for muscle GYS1 versus liver GYS2 homology.,sequence_specificity_and_offtarget_design_context, CTRL_POS_DDC_CHOLESTATIC_LIVER_INJURY_ALT_ALP_BILI,positive_control_cholestatic_liver_injury,,,,,,dbbun_generated,CC BY 4.0,,,OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,"Positive hepatobiliary injury context representing DDC-induced cholestasis with elevated ALP, ALT, bilirubin, cholesterol, portal inflammation, ductular reaction, and fibrosis.",,high_cholestatic_liver_injury_signal CTRL_NEG_CHOLESTASIS_RECOVERY_R15_RESOLUTION,negative_control_recovery_resolution,,,,,,dbbun_generated,CC BY 4.0,,,OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,Recovery/resolution context representing return toward baseline liver chemistry and reduced cholangiocyte inflammatory signaling after DDC withdrawal.,,resolved_or_low_cholestatic_liver_injury_signal CTRL_CONTEXT_CX3CL1_CX3CR1_MACROPHAGE_RECRUITMENT,mechanism_context_control,,,,,,dbbun_generated,CC BY 4.0,,,OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,Context control representing cholangiocyte CX3CL1 expression and periportal CX3CR1-positive macrophage recruitment during cholestatic injury.,,cholangiocyte_macrophage_interaction_context CTRL_CONTEXT_NFYA_TGFB1_CHOLANGIOCYTE_FIBROSIS,mechanism_context_control,,,,,,dbbun_generated,CC BY 4.0,,,OLSON_CHOLANGIOCYTE_CHOLESTASIS_2025,Context control representing NF-YA activation in cholangiocytes and siRNA NF-YA suppression reducing TGFβ1 expression in normal human cholangiocytes.,,cholangiocyte_fibrosis_TGFB1_context CTRL_NEG_PCDHA11_AMNA_2255_LOW_REVERSIBLE_LIVER_SIGNAL,negative_control_low_sequence_dependent_AmNA_ASO_liver_signal,,,,,inferred_from_paper,dbbun_generated,CC BY 4.0,,,KANDA_PCDHA11_AMNA_ASO_2024,Generated hPCDHA11-2255-like AmNA-ASO control with lower modeled AST/ALT signal and strong recovery after treatment cessation.,low_to_moderate_reversible_liver_signal_with_target_knockdown_context, CTRL_NEG_PCDHA11_AMNA_3319_LOW_OFFTARGET_LIVER_SIGNAL,negative_control_lower_offtarget_AmNA_ASO_liver_signal,,,,,inferred_from_paper,dbbun_generated,CC BY 4.0,,,KANDA_PCDHA11_AMNA_ASO_2024,"Generated hPCDHA11-3319-like AmNA-ASO control representing lower off-target risk, target knockdown, antitumor activity, and reversible low-to-moderate liver-enzyme response.",lower_offtarget_burden_and_reversible_liver_signal, CTRL_POS_PCDHA11_AMNA_3969_SEQUENCE_DEPENDENT_LIVER_INJURY,positive_control_sequence_dependent_AmNA_ASO_hepatotoxicity,,,,,inferred_from_paper,dbbun_generated,CC BY 4.0,,,KANDA_PCDHA11_AMNA_ASO_2024,Generated hPCDHA11-3969-like AmNA-ASO positive control representing stronger sequence-dependent AST/ALT elevation and higher off-target/mismatch-burden context.,high_reversible_sequence_dependent_liver_injury_signal, CTRL_CONTEXT_PCDHA11_AMNA_OFFTARGET_MICROARRAY_SCREEN,context_control_offtarget_bioinformatics_microarray_screening,,,,,inferred_from_paper,dbbun_generated,CC BY 4.0,,,KANDA_PCDHA11_AMNA_ASO_2024,Context control for combined in silico mismatch search and microarray perturbation screening of AmNA-modified anti-PCDHA11 ASOs.,offtarget_screening_and_transcriptomic_perturbation_context, CTRL_CONTEXT_PCDHA11_KO_TARGET_SPECIFICITY_APOPTOSIS,context_control_target_specificity_and_apoptosis,,,,,inferred_from_paper,dbbun_generated,CC BY 4.0,,,KANDA_PCDHA11_AMNA_ASO_2024,Context control representing target-specificity evidence: attenuated ASO effect in PCDHA11-knockout cells and apoptosis/caspase response in parental PCDHA11-expressing cells.,target_specificity_and_on_target_pharmacology_context, CTRL_POS_PS_ASO_DDR_HIGH_CONDENSATE,positive_control_PS_ASO_DNA_damage_response_toxicity,PS_backbone_concentration_dependent_repair_enzyme_condensate_high_risk,"high PS-body/condensate formation, DNA-PKcs/ATM/PARP1 binding, checkpoint activation, HR suppression, and toxic DNA-lesion proxy",Represents a high-PS gapmer/ASO condition that activates DNA damage response without requiring DNA breaks.,HJELMGREN_PS_ASO_DDR_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_PO_ASO_LOW_DDR_NO_PS_BODY,negative_control_PO_backbone_low_DDR,phosphodiester_or_low_PS_backbone_contrast,low PS-body/filament formation and low repair-enzyme condensate activation,Represents the PS-backbone requirement by contrasting PO/low-PS oligo context with PS-ASO conditions.,HJELMGREN_PS_ASO_DDR_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ASO_REPAIR_PROTEIN_BINDING,mechanism_context_control_ASO_repair_protein_binding,DNA-PKcs_ATM_PARPs_binding_and_phase_separation_context,repair proteins bind ASO polymers and form nuclear condensate-like structures,Documents the mechanism layer connecting ASO chemistry to repair-enzyme activation and cellular toxicity.,HJELMGREN_PS_ASO_DDR_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_SIRUBICON_ROS_GALNAC_LIVER_FUNCTION_IMPROVED,negative_control_ROS_responsive_GalNAc_siRNA_liver_function_improvement,targeted_siRubicon_MASH_low_hepatotoxicity_liver_function_context,"Rubicon knockdown, increased lipophagy, reduced steatosis, lower generated ALT/AST, and higher albumin context",Represents disease-responsive hepatocyte-targeted siRNA delivery with liver-function improvement rather than intrinsic liver injury.,LAN_SIRUBICON_ROS_GALNAC_MASH_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ROS_GALNAC_HEPATOCYTE_TARGETING,delivery_context_control_ROS_GalNAc_hepatocyte_targeting,oxidative_stress_triggered_shell_disassembly_ASGPR_hepatocyte_targeting,"higher liver/MASH accumulation, ASGPR-mediated hepatocyte uptake, and lower non-parenchymal Rubicon suppression context",Represents the dual targeting mechanism: ROS-responsive liver activation plus GalNAc/ASGPR hepatocyte uptake.,LAN_SIRUBICON_ROS_GALNAC_MASH_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_PEI_NANOCARRIER_SAFETY_MONITORING,delivery_safety_context_control_PEI_nanocarrier,cationic_vector_and_offtarget_organ_retention_safety_monitoring,"delivery benefit with explicit monitoring of PEI-related cytotoxicity, organ distribution, immune clearance, ALT/AST, and albumin context",Represents the need to monitor cationic PEI and nanoparticle delivery risks even when therapeutic liver readouts improve.,LAN_SIRUBICON_ROS_GALNAC_MASH_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_SCPBNA2_ASO_LOW_HEPATOTOX_RETAINED_KD,negative_control_scpBNA2_gapmer_low_hepatotoxicity,negative_control_scpBNA2_gapmer_low_hepatotoxicity,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_LNA_BNA_ASO_HEPATOTOX_PARENT,positive_control_LNA_BNA_parent_ASO_hepatotoxicity,positive_control_LNA_BNA_parent_ASO_hepatotoxicity,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_REDUCED_PS_PO_LINKAGE_LOWER_ACTIVITY_RISK,context_control_reduced_PS_PO_linkage_tradeoff,context_control_reduced_PS_PO_linkage_tradeoff,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,YAMAGUCHI_SCPBNA2_REDUCED_HEPATOTOX_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_SICYP2E1_LNP_APAP_ALT_AST_RESCUE,negative_control_siCyp2e1_LNP_APAP_rescue,negative_control_siCyp2e1_LNP_APAP_rescue,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,LIU_CYP2E1_LNP_APAP_AILI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_APAP_AILI_UNTREATED_HIGH_ALT_AST,positive_control_APAP_acute_liver_injury,positive_control_APAP_acute_liver_injury,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,LIU_CYP2E1_LNP_APAP_AILI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_DELAYED_SICYP2E1_LIMITED_EARLY_RESCUE_RECOVERY,context_control_delayed_siCyp2e1_timing_dependence,context_control_delayed_siCyp2e1_timing_dependence,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,LIU_CYP2E1_LNP_APAP_AILI_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_CHOLESTEROL_NANP_HEPATOCYTE_UPTAKE,delivery_context_control_cholesterol_NANP_hepatocyte_uptake,delivery_context_control_cholesterol_NANP_hepatocyte_uptake,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,KIM_NANP_LIPID_LIVER_TARGETING_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_TRIGALNAC_NANP_WEAK_ASGPR_UPTAKE,delivery_context_control_TriGalNAc_NANP_ASGPR_contrast,delivery_context_control_TriGalNAc_NANP_ASGPR_contrast,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,KIM_NANP_LIPID_LIVER_TARGETING_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_NANP_KUPFFER_SCAVENGER_ASSOCIATION,positive_control_NANP_Kupffer_macrophage_association,positive_control_NANP_Kupffer_macrophage_association,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper.,KIM_NANP_LIPID_LIVER_TARGETING_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_RNA_NP_NON_TARGETED_LOW_OFFTARGET,negative_control_non_targeted_RNA_nanoparticle_low_offtarget,negative_control_non_targeted_RNA_nanoparticle_low_offtarget,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_RNA_NP_MULTITARGET_HCC_ACTIVITY,context_control_RNA_nanoparticle_multitarget_HCC_activity,context_control_RNA_nanoparticle_multitarget_HCC_activity,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_RNA_NP_VERO_DOSE_WINDOW,context_control_RNA_nanoparticle_non_cancer_dose_window,context_control_RNA_nanoparticle_non_cancer_dose_window,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,SUN_HCC_RNA_NANOPARTICLE_MULTITARGET_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_DCA_ASIRNA_NO_VISIBLE_TOX_DURABLE_KD,negative_control_DCA_asiRNA_visible_tolerability_durable_knockdown,negative_control_DCA_asiRNA_visible_tolerability_durable_knockdown,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ASIRNA_SEED_OFFTARGET_REDUCTION,context_control_asymmetric_siRNA_seed_offtarget_reduction,context_control_asymmetric_siRNA_seed_offtarget_reduction,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_HEAVY_2F_PS_MODIFICATION_OFFTARGET_RISK,context_control_heavy_2primeF_PS_modification_offtarget_risk,context_control_heavy_2primeF_PS_modification_offtarget_risk,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,MEKONNEN_MYC_ASIRNA_DCA_TNBC_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_MULTIFUNCTIONAL_HDO_DELIVERY,context_control_multifunctional_HDO_delivery,context_control_multifunctional_HDO_delivery,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,SOUSA_HDO_MULTIFUNCTIONAL_HELA_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_HDO_SCRAMBLED_CONTROL,negative_control_HDO_scrambled_sequence,negative_control_HDO_scrambled_sequence,generated v1.0 control behavior,Focused benchmark/control for the encoded source paper and judging-criteria evidence layer.,SOUSA_HDO_MULTIFUNCTIONAL_HELA_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_AGT_GALNAC_SIRNA_SAFE_CANDIDATE,negative_control_AGT_GalNAc_siRNA_safe_candidate,negative_control_AGT_GalNAc_siRNA_safe_candidate,low ALT/AST/urea and favorable RNAseq off-target profile,Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_AGT_SIRNA_OFFTARGET_LIVER_KIDNEY_SIGNAL,positive_control_AGT_siRNA_offtarget_liver_kidney_signal,positive_control_AGT_siRNA_offtarget_liver_kidney_signal,elevated ALT/AST/urea and histopathology risk due to dose-dependent off-target transcript effects,Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ZILEBESIRAN_LIKE_COMPARATOR,context_control_Zilebesiran_like_AGT_siRNA_comparator,context_control_Zilebesiran_like_AGT_siRNA_comparator,"benchmark comparator for AGT knockdown, durability, and BP-reduction context",Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,HUANG_AGT_GALNAC_SIRNA_TOXICOLOGY_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_CPG_ODN_MACROPHAGE_APAP_PROTECTION,negative_control_CpG_ODN_macrophage_APAP_protection,negative_control_CpG_ODN_macrophage_APAP_protection,reduced APAP injury through macrophage TLR9/IRG1/itaconate context,Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,QU_CPG_ODN_APAP_TLR9_IRG1_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_CPG_ODN_ACOD1_SIRNA_LOSS_OF_PROTECTION,positive_control_CpG_ODN_Acod1_siRNA_loss_of_protection,positive_control_CpG_ODN_Acod1_siRNA_loss_of_protection,loss of itaconate-mediated protection after Acod1/IRG1 interference,Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,QU_CPG_ODN_APAP_TLR9_IRG1_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ERBB2_APTAMER_PET_PK_BIODISTRIBUTION,context_control_ERBB2_aptamer_PET_PK_biodistribution,context_control_ERBB2_aptamer_PET_PK_biodistribution,organ PK/biodistribution and excretion context for oligonucleotide-based drugs,Focused v1.0 benchmark/control for source-specific judging-criteria demonstration.,PARK_ERBB2_APTAMER_PET_PK_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_PARENT_LNA_GAPMER_ALT_SIGNAL,positive_control_parent_LNA_gapmer_ALT_signal,positive_control_parent_LNA_gapmer_ALT_signal,parent fully PS LNA gapmer retains activity but raises ALT/body-weight toxicity signal,Focused v1.0 benchmark/control for challenge-aligned source-specific demonstration.,TERADA_BROTHERS_ASO_PNA_TOEHOLD_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_BROTHERS_ASO_PNA_ALT_MITIGATION,negative_control_BROTHERS_ASO_PNA_toxicity_mitigation,negative_control_BROTHERS_ASO_PNA_toxicity_mitigation,BRO duplex retains knockdown while reducing protein/off-target interactions and ALT elevation,Focused v1.0 benchmark/control for challenge-aligned source-specific demonstration.,TERADA_BROTHERS_ASO_PNA_TOEHOLD_2023,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_APOC3_GALNAC_SIRNA_LONG_ACTING_SAFE,negative_control_APOC3_long_acting_GalNAc_siRNA,negative_control_APOC3_long_acting_GalNAc_siRNA,durable APOC3 lowering with favorable selectivity and tolerability,Focused v1.0 benchmark/control for challenge-aligned source-specific demonstration.,PRAKASH_APOC3_LONG_ACTING_GALNAC_SIRNA_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_GALNAC_SIRNA_LCMS_BIOANALYSIS,context_control_GalNAc_siRNA_LCMS_bioanalysis,context_control_GalNAc_siRNA_LCMS_bioanalysis,LC/MS quantification module for parent/metabolite PK and reproducibility,Focused v1.0 benchmark/control for challenge-aligned source-specific demonstration.,KIM_GALNAC_SIRNA_LCMS_DPPT_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_ORAL_MIR29A_FIBROSIS_NA,context_control_oral_miR29a_like_liver_fibrosis_NA,context_control_oral_miR29a_like_liver_fibrosis_NA,modified nuclease-resistant oral NA suppresses fibrosis markers in CCl4 liver-injury context,Focused v1.0 benchmark/control for challenge-aligned source-specific demonstration.,UMEZU_ORAL_MIR29A_LIVER_FIBROSIS_NA_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_LNP_CRISPR_HAO1_NO_LIVER_TOX_LONG_TERM,negative_control_LNP_CRISPR_HAO1_long_term_liver_safety,negative_control_LNP_CRISPR_HAO1_long_term_liver_safety,"single-dose LNP-CRISPR HAO1/Hao1 context shows durable effect with low off-target, liver-toxicity, and immune-response signals",Focused v1.0 control for challenge-aligned source-specific demonstration.,JIANG_LNP_CRISPR_HAO1_PH1_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_PS_LNA_ASO_INTERNALIZATION_LOW_TOX,context_control_PS_LNA_ASO_internalization_tolerability,context_control_PS_LNA_ASO_internalization_tolerability,"vehicle-free PS/LNA ASO context with cell-uptake, viability, and cytoplasmic internalization measurements",Focused v1.0 control for challenge-aligned source-specific demonstration.,GOTFRID_PS_LNA_HIV_ASO_ACTIVITY_2026,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_ESCPLUS_SEED_DESTABILIZED_LOW_ALT,negative_control_ESCplus_seed_pairing_destabilized_GalNAc_siRNA_low_ALT,negative_control_ESCplus_seed_pairing_destabilized_GalNAc_siRNA_low_ALT,single GNA or 2-5-RNA seed-region destabilization reduces seed-mediated off-target interaction while preserving on-target activity and lowering ALT liability,Focused v1.0 control for challenge-aligned source-specific demonstration.,SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_ESC_PARENT_SEED_OFFTARGET_ALT,positive_control_parent_ESC_GalNAc_siRNA_seed_offtarget_ALT,positive_control_parent_ESC_GalNAc_siRNA_seed_offtarget_ALT,parent ESC GalNAc-siRNA context with seed-mediated off-target hepatotoxicity and ALT elevation risk,Focused v1.0 control for challenge-aligned source-specific demonstration.,SCHLEGEL_ESCPLUS_SEED_PAIRING_GALNAC_SIRNA_2022,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_LNA_PTTE_BACKBONE_ACTIVITY,context_control_LNA_phosphothiotriester_backbone_activity,context_control_LNA_phosphothiotriester_backbone_activity,charge-neutral LNA-phosphothiotriester SSO chemistry with duplex stability and splice-switching activity context,Focused v1.0 control for challenge-aligned source-specific demonstration.,DHARA_LNA_PHOSPHOTHIOTRIESTER_SSO_CLICK_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_FXR_G0S2_DILI_RESCUE,context_control_FXR_G0S2_metabolic_DILI_rescue,context_control_FXR_G0S2_metabolic_DILI_rescue,FXR/JNK/G0s2 hepatotoxicity pathway context where pathway modulation reduces liver-injury and metabolic-disorder signals,Focused v1.0 control for challenge-aligned source-specific demonstration.,LI_FXR_JNK_G0S2_TRIPTOLIDE_HEPATOTOXICITY_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_POS_HIGH_AFFINITY_GAPMER_RNASEH1_LONG_PREMRNA_ALT,positive_control_high_affinity_gapmer_RNaseH1_very_long_pre_mRNA_ALT,positive_control_high_affinity_gapmer_RNaseH1_very_long_pre_mRNA_ALT,high-affinity LNA/cEt-like gapmer context with promiscuous RNase H1-dependent reduction of very long pre-mRNAs and ALT/AST liability,Focused v1.0 control for challenge-aligned source-specific demonstration.,BUREL_GAPMER_RNASEH1_LONG_PREMRNA_HEPATOTOX_2016,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_NEG_MOE_OR_RNASEH1_ATTENUATED_GAPMER,negative_control_MOE_or_RNaseH1_attenuated_gapmer_low_ALT,negative_control_MOE_or_RNaseH1_attenuated_gapmer_low_ALT,MOE-like or RNase-H1-attenuated context with lower very-long-pre-mRNA off-target reduction and lower transaminase liability,Focused v1.0 control for challenge-aligned source-specific demonstration.,BUREL_GAPMER_RNASEH1_LONG_PREMRNA_HEPATOTOX_2016,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_QC_FREE_ASO_PAYLOAD_LCMS_SPECIFICITY,measurement_control_free_ASO_payload_LCMS_specificity,measurement_control_free_ASO_payload_LCMS_specificity,"hybridization LC-MS/MS context separating free ASO payload from intact conjugate, linker-bearing ASO, and metabolites",Focused v1.0 control for challenge-aligned source-specific demonstration.,JIANG_AOC_FREE_ASO_PAYLOAD_HYBRIDIZATION_LCMS_2024,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,, CTRL_CONTEXT_PUM1_EXOSOME_HSC_FIBROSIS_AXIS,context_control_PUM1_exosome_HSC_fibrosis_axis,context_control_PUM1_exosome_HSC_fibrosis_axis,PUM1-enriched hepatocyte exosome context suppressing TPM4 translation and HSC activation; PUM1 loss aggravates MASLD liver injury,Focused v1.0 control for challenge-aligned source-specific demonstration.,WAN_PUM1_EXOSOMES_MASLD_HSC_FIBROSIS_2025,inferred_from_paper,dbbun_generated,CC BY 4.0,,,,,,