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Investigating the pharmacodynamic durability of GalNAc–siRNA conjugates

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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo**

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The Late Endosome and Its Lipid BMP Act as Gateways for Efficient Cytosolic Access of the Delivery Agent dfTAT and Its Macromolecular Cargos

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Fusogenic peptides enhance endosomal escape improving siRNA-induced silencing of oncogenes

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Endosomal escape pathways for delivery of biologicals

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Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate

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Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA Conjugates

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Catabolism of Desialylated Ceruloplasmin in the Liver

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Facile Synthesis, Geometry, and 2′-Substituent-Dependent in Vivo Activity of 5′-(E)- and 5′-(Z)-Vinylphosphonate-Modified siRNA Conjugates

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siRNA Conjugates Carrying Sequentially Assembled Trivalent N-Acetylgalactosamine Linked Through Nucleosides Elicit Robust Gene Silencing In Vivo in Hepatocytes

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Multivalent N -Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing

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Long-lived microRNA–Argonaute complexes in quiescent cells can be activated to regulate mitogenic responses

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Biochemical isolation of Argonaute protein complexes by Ago-APP

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siRNA carrying an (E)-vinylphosphonate moiety at the 5΄ end of the guide strand augments gene silencing by enhanced binding to human Argonaute-2

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Intra-endosomal trafficking mediated by lysobisphosphatidic acid contributes to intracellular release of phosphorothioate-modified antisense oligonucleotides

inferredcites →https://doi.org/10.1093/nar/gkx818openalex-snapshot

Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc–siRNA conjugates

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Real-time quantification of microRNAs by stem-loop RT-PCR

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Targeted mRNA degradation by double-stranded RNA in vitro

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Mammalian Hepatic Lectin

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Argonaute proteins regulate microRNA stability: Increased microRNA abundance by Argonaute proteins is due to microRNA stabilization

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inferred← citeshttps://doi.org/10.1016/j.molimm.2023.07.010openalex-snapshot

Liver factor B silencing to cure C3 glomerulopathy: Evidence from a mouse model of complement dysregulation

inferred← citeshttps://doi.org/10.1016/j.molmed.2023.10.005openalex-snapshot

Three ‘E’ challenges for siRNA drug development

inferred← citeshttps://doi.org/10.1016/j.nano.2022.102564openalex-snapshot

Galactose-modified nanoparticles for delivery of microRNA to mitigate the progress of abdominal aortic aneurysms via regulating macrophage polarization

inferred← citeshttps://doi.org/10.1016/j.nantod.2022.101514openalex-snapshot

Non-viral nucleic acid therapeutics: Revolutionizing the landscape of atherosclerotic treatment

inferred← citeshttps://doi.org/10.1016/j.nxnano.2025.100135openalex-snapshot

siRNA therapeutics for effective management of rheumatoid arthritis

inferred← citeshttps://doi.org/10.1016/j.omtm.2025.101466openalex-snapshot

Species-specific gene expression manipulation in humanized livers of chimeric mice via siRNA-encapsulated lipid nanoparticle treatment

inferred← citeshttps://doi.org/10.1016/j.omtn.2021.07.018openalex-snapshot

Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids

inferred← citeshttps://doi.org/10.1016/j.omtn.2023.01.005openalex-snapshot

Identification of potent siRNA targeting complement C5 and its robust activity in pre-clinical models of myasthenia gravis and collagen-induced arthritis

inferred← citeshttps://doi.org/10.1016/j.omtn.2023.07.019openalex-snapshot

Chloroquine and cytosolic galectins affect endosomal escape of antisense oligonucleotides after Stabilin-mediated endocytosis

inferred← citeshttps://doi.org/10.1016/j.omtn.2024.102195openalex-snapshot

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges

inferred← citeshttps://doi.org/10.1016/j.omtn.2024.102230openalex-snapshot

Phosphatidylcholine head group chemistry alters the extrahepatic accumulation of lipid-conjugated siRNA

inferred← citeshttps://doi.org/10.1016/j.omtn.2025.102516openalex-snapshot

Mechanistic intracellular PK/PD modeling to inform development strategies for small interfering RNA therapeutics

inferred← citeshttps://doi.org/10.1016/j.omtn.2025.102590openalex-snapshot

Realizing the therapeutic potential of rapid knockdown of transthyretin via RNA interference in transthyretin amyloidosis

inferred← citeshttps://doi.org/10.1016/j.pmatsci.2025.101436openalex-snapshot

Breaking through barrier: The emerging role of nucleic acids-based drug delivery in stroke

inferred← citeshttps://doi.org/10.1016/j.trechm.2025.10.002openalex-snapshot

Functional bioconjugates for precision delivery of nucleic acid therapeutics

inferred← citeshttps://doi.org/10.1016/j.treopn.2026.08.019openalex-snapshot

Antibody–oligonucleotide conjugates advance targeted RNA delivery

inferred← citeshttps://doi.org/10.1016/j.vesic.2025.100094openalex-snapshot

Encapsulating extracellular vesicles with a minimal RISC complex as novel gene silencing tool

inferred← citeshttps://doi.org/10.1016/j.xcrm.2025.102524openalex-snapshot

Engineered Akkermansia muciniphila vesicles for targeted pyroptosis and trained immunity to enhance immunotherapy in hepatocellular carcinoma

inferred← citeshttps://doi.org/10.1016/j.xphs.2023.10.026openalex-snapshot

Mechanistic Pharmacokinetics and Pharmacodynamics of GalNAc-siRNA: Translational Model Involving Competitive Receptor-Mediated Disposition and RISC-Dependent Gene Silencing Applied to Givosiran

inferred← citeshttps://doi.org/10.1016/j.ymthe.2021.06.002openalex-snapshot

Ligand conjugate SAR and enhanced delivery in NHP

inferred← citeshttps://doi.org/10.1016/j.ymthe.2022.04.019openalex-snapshot

RNAi-based modulation of IFN-γ signaling in skin

inferred← citeshttps://doi.org/10.1016/j.ymthe.2022.09.009openalex-snapshot

Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infection

inferred← citeshttps://doi.org/10.1016/j.ymthe.2023.01.005openalex-snapshot

RNA editing: Expanding the potential of RNA therapeutics

inferred← citeshttps://doi.org/10.1016/j.ymthe.2023.11.012openalex-snapshot

GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma

inferred← citeshttps://doi.org/10.1016/j.ymthe.2025.08.017openalex-snapshot

Optimized chemical structure extends silencing duration of therapeutic siRNAs in dividing cancer and immune cells

inferred← citeshttps://doi.org/10.1016/j.ymthe.2025.09.041openalex-snapshot

Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art

inferred← citeshttps://doi.org/10.1016/s0140-6736(26)01639-9openalex-snapshot

Deep and durable lipoprotein(a) lowering: Kylo-11 advances RNA interference therapeutics

inferred← citeshttps://doi.org/10.1021/acs.bioconjchem.4c00079openalex-snapshot

Revival of Bioengineered Proteins as Carriers for Nucleic Acids

inferred← citeshttps://doi.org/10.1021/acs.bioconjchem.5c00069openalex-snapshot

Multiprotein Silencing Using WRAP-Based Nanoparticles: A Proof of Concept

inferred← citeshttps://doi.org/10.1021/acs.bioconjchem.5c00156openalex-snapshot

Multimeric Conjugates Using Engineered Peptide Scaffolds for Efficient siRNA Delivery

inferred← citeshttps://doi.org/10.1021/acs.bioconjchem.5c00212openalex-snapshot

Exploring the Potentials of Antibody–siRNA Conjugates in Tumor Cell Gene Silencing without Cationic Assistance

inferred← citeshttps://doi.org/10.1021/acs.bioconjchem.6c00339openalex-snapshot

Synthesis and Characterization of Aminooxy Click Chemistry-Mediated Bis -Conjugates of siRNAs and Evaluation of Their RNAi Activity

inferred← citeshttps://doi.org/10.1021/acs.chemrev.4c00472openalex-snapshot

Technologies for Targeted RNA Degradation and Induced RNA Decay

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.1c00144openalex-snapshot

Syntheses of Morpholine-Based Nucleotide Analogs for Hepatic siRNA Targeting and Stabilization

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.2c00502openalex-snapshot

Design and Measurement of Drug Tissue Concentration Asymmetry and Tissue Exposure-Effect (Tissue PK-PD) Evaluation

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.2c01337openalex-snapshot

Metabolically Stable Anomeric Linkages Containing GalNAc–siRNA Conjugates: An Interplay among ASGPR, Glycosidase, and RISC Pathways

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.4c00802openalex-snapshot

Structure–Activity Relationship of Antibody–Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody–siRNA Conjugates for Drug Development

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.4c02528openalex-snapshot

Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver

inferred← citeshttps://doi.org/10.1021/acs.molpharmaceut.3c00561openalex-snapshot

A Modular Albumin-Oligonucleotide Biomolecular Assembly for Delivery of Antisense Therapeutics

inferred← citeshttps://doi.org/10.1021/acs.molpharmaceut.3c01158openalex-snapshot

Recent Progress of Small Interfering RNA Delivery on the Market and Clinical Stage

inferred← citeshttps://doi.org/10.1021/acs.molpharmaceut.5c01925openalex-snapshot

Ionizable Polymeric Micelles Targeting Transferrin Receptor 1 Enhance Systemic mRNA Delivery to the Brain

inferred← citeshttps://doi.org/10.1021/acs.oprd.5c00122openalex-snapshot

Novel and Practical Synthesis of Triantennary N-Acetylgalactosamine Ligands for Liver-Targeted Delivery of siRNA Therapeutics

inferred← citeshttps://doi.org/10.1021/acs.orglett.2c00988openalex-snapshot

Aminooxy Click Chemistry as a Tool for Bis-homo and Bis-hetero Ligand Conjugation to Nucleic Acids

inferred← citeshttps://doi.org/10.1021/acsami.3c15424openalex-snapshot

Which Lipid Nanoparticle (LNP) Designs Work? A Simple Kinetic Model Linking LNP Chemical Structure to In Vivo Delivery Performance

inferred← citeshttps://doi.org/10.1021/acsami.5c24581openalex-snapshot

Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting

inferred← citeshttps://doi.org/10.1021/acsbiomedchemau.4c00092openalex-snapshot

Nucleic Acid Conjugates: Unlocking Therapeutic Potential

inferred← citeshttps://doi.org/10.1021/acschembio.3c00612openalex-snapshot

Cellular Penetration and Intracellular Dynamics of Perfluorocarbon-Conjugated DNA/RNA as a Potential Means of Conditional Nucleic Acid Delivery

inferred← citeshttps://doi.org/10.1021/acsnano.1c05099openalex-snapshot

Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles

inferred← citeshttps://doi.org/10.1021/acsnano.3c01199openalex-snapshot

Long Noncoding RNA URB1-Antisense RNA 1 (AS1) Suppresses Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma by Driving Ferritin Phase Separation

inferred← citeshttps://doi.org/10.1021/acsnano.4c18345openalex-snapshot

Treatment of Acute Liver Injury through Selective Tropism of High Mobility Group Box 1 Gene-Silenced Large Peritoneal Macrophages

inferred← citeshttps://doi.org/10.1021/acsnano.5c18112openalex-snapshot

The Biology of Endosomal Escape: Strategies for Enhanced Delivery of Therapeutics

inferred← citeshttps://doi.org/10.1021/acsomega.1c01755openalex-snapshot

Liver-Targeted Delivery of Oligonucleotides with N-Acetylgalactosamine Conjugation

inferred← citeshttps://doi.org/10.1021/acsomega.4c11519openalex-snapshot

Improving the Cellular Accumulation of Folate-Conjugated Fully Chemically Modified siRNAs via 3′ Terminal Conjugation

inferred← citeshttps://doi.org/10.1021/acsomega.6c04146openalex-snapshot

A Dual-Halogen Labeling Strategy to Detect and Quantify Double-Stranded RNAs Using NanoSIMS: A Proof-of-Concept Study

inferred← citeshttps://doi.org/10.1021/jacs.3c07023openalex-snapshot

Exceptional Nuclease Resistance of DNA and RNA with the Addition of Small-Molecule Nucleobase Mimics

inferred← citeshttps://doi.org/10.1021/jacs.4c00691openalex-snapshot

Engineering Biomimetic Protein Camouflage for Delivering Peptide/siRNA Nanocomplexes

inferred← citeshttps://doi.org/10.1021/jacs.5c02986openalex-snapshot

UV-Cross-Linked DNA Nanomaterials Enable Robust Nanopatterning of Folate Ligands for Enhanced Cellular Uptake

inferred← citeshttps://doi.org/10.1021/jacsau.5c00012openalex-snapshot

General Platform for Efficient and Modular Assembly of GalNAc–siRNA Conjugates via Primary Amines and o-Nitrobenzyl Alcohol Cyclization Photoclick Chemistry Enabling Rapid Access to Therapeutic Oligonucleotides

inferred← citeshttps://doi.org/10.1038/s41388-023-02801-8openalex-snapshot

A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy

inferred← citeshttps://doi.org/10.1038/s41392-024-02035-4openalex-snapshot

Nucleic acid drugs: recent progress and future perspectives

inferred← citeshttps://doi.org/10.1038/s41419-025-07401-wopenalex-snapshot

The liver-specific long noncoding RNA FAM99B inhibits ribosome biogenesis and cancer progression through cleavage of dead-box Helicase 21

inferred← citeshttps://doi.org/10.1038/s41434-026-00621-5openalex-snapshot

Research progress and development strategies of antibody-oligonucleotide conjugates

inferred← citeshttps://doi.org/10.1038/s41467-022-33061-xopenalex-snapshot

Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington’s disease models

inferred← citeshttps://doi.org/10.1038/s41467-023-36752-1openalex-snapshot

Single-cell quantification and dose-response of cytosolic siRNA delivery

inferred← citeshttps://doi.org/10.1038/s41467-023-37774-5openalex-snapshot

RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes

inferred← citeshttps://doi.org/10.1038/s41467-024-45609-0openalex-snapshot

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy

inferred← citeshttps://doi.org/10.1038/s41565-021-00898-0openalex-snapshot

The current landscape of nucleic acid therapeutics

inferred← citeshttps://doi.org/10.1038/s41573-022-00407-5openalex-snapshot

Therapeutic RNA-silencing oligonucleotides in metabolic diseases

inferred← citeshttps://doi.org/10.1038/s41573-024-00912-9openalex-snapshot

RNAi-based drug design: considerations and future directions

inferred← citeshttps://doi.org/10.1038/s41573-024-00943-2openalex-snapshot

Frameworks for transformational breakthroughs in RNA-based medicines

inferred← citeshttps://doi.org/10.1038/s41573-024-01086-0openalex-snapshot

Chemical engineering of CRISPR–Cas systems for therapeutic application

inferred← citeshttps://doi.org/10.1038/s41587-023-01927-0openalex-snapshot

Precision RNA base editing with engineered and endogenous effectors

inferred← citeshttps://doi.org/10.1038/s41587-023-02105-yopenalex-snapshot

RNA interference in the era of nucleic acid therapeutics

inferred← citeshttps://doi.org/10.1038/s41587-024-02336-7openalex-snapshot

Enhancing siRNA efficacy in vivo with extended nucleic acid backbones

inferred← citeshttps://doi.org/10.1038/s42003-022-03132-2openalex-snapshot

Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides

inferred← citeshttps://doi.org/10.1039/9781837671328-00350openalex-snapshot

Nucleic Acid Therapeutics

inferred← citeshttps://doi.org/10.1039/d0cc06285eopenalex-snapshot

Delivery of siRNA by tailored cell-penetrating urea-based foldamers

inferred← citeshttps://doi.org/10.1039/d0ra07747jopenalex-snapshot

Chemical strategies for strand selection in short-interfering RNAs

inferred← citeshttps://doi.org/10.1039/d2ra00705copenalex-snapshot

Synthesis, gene silencing activity, thermal stability, and serum stability of siRNA containing four ( S )-5′- C -aminopropyl-2′- O -methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine)

inferred← citeshttps://doi.org/10.1039/d2ra01999jopenalex-snapshot

Beyond GalNAc! Drug delivery systems comprising complex oligosaccharides for targeted use of nucleic acid therapeutics

inferred← citeshttps://doi.org/10.1039/d4md00652fopenalex-snapshot

Hepatocyte targeting via the asialoglycoprotein receptor

inferred← citeshttps://doi.org/10.1039/d6cb00037aopenalex-snapshot

Current landscape of RNA chemistry and delivery in cancer immunotherapy

inferred← citeshttps://doi.org/10.1039/d6tb00411copenalex-snapshot

Recent innovative approaches for drug delivery systems targeting cancer and CNS disorders

inferred← citeshttps://doi.org/10.1080/14728222.2026.2748740openalex-snapshot

Molecular basis for developing tumor-targeted siRnas for future immunotherapy

inferred← citeshttps://doi.org/10.1080/15476286.2022.2027150openalex-snapshot

Innovative developments and emerging technologies in RNA therapeutics

inferred← citeshttps://doi.org/10.1080/15476286.2023.2196046openalex-snapshot

Small regulatory RNAs: from bench to bedside – a keystone symposia meeting report

inferred← citeshttps://doi.org/10.1080/17425247.2024.2409142openalex-snapshot

Evaluating the breadth of nucleic acid-based payloads delivered in lipid nanoparticles to establish fundamental differences in development

inferred← citeshttps://doi.org/10.1080/17425247.2025.2466767openalex-snapshot

GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases

inferred← citeshttps://doi.org/10.1080/17435889.2025.2555507openalex-snapshot

Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery

inferred← citeshttps://doi.org/10.1080/17512433.2023.2277330openalex-snapshot

Emerging insights and future prospects for therapeutic application of siRNA targeting angiotensinogen in hypertension

inferred← citeshttps://doi.org/10.1080/17576180.2025.2548194openalex-snapshot

Examining hybridization-based LC–MS methodologies for the bioanalysis of siRNA analytes

inferred← citeshttps://doi.org/10.1080/17576180.2025.2554565openalex-snapshot

Upgrading nucleic acid and antisense therapeutics: challenges, solutions, and future directions

inferred← citeshttps://doi.org/10.1089/nat.2020.0919openalex-snapshot

Impact of Serum Proteins on the Uptake and RNAi Activity of GalNAc-Conjugated siRNAs

inferred← citeshttps://doi.org/10.1089/nat.2021.0085openalex-snapshot

Challenges and Opportunities for Nucleic Acid Therapeutics

inferred← citeshttps://doi.org/10.1089/nat.2021.29004.otsopenalex-snapshot

17th Annual Meeting of the Oligonucleotide Therapeutics Society: A Tribute to Bob Letsinger, Progress in N = 1 Treatments, and Successful First In-Humans CRISPR Trials

inferred← citeshttps://doi.org/10.1089/nat.2022.0004openalex-snapshot

Delivery of RNA Therapeutics: The Great Endosomal Escape!

inferred← citeshttps://doi.org/10.1089/nat.2022.0038openalex-snapshot

Cholesterol-Conjugated siRNA Silencing Tnf for the Treatment of Liver Macrophage-Mediated Acute Inflammation in Nonalcoholic Fatty Liver Disease

inferred← citeshttps://doi.org/10.1089/nat.2022.0061openalex-snapshot

Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides

inferred← citeshttps://doi.org/10.1089/nat.2024.0031openalex-snapshot

A Guide to Chemical Considerations for the Pre-Clinical Development of Oligonucleotides

inferred← citeshttps://doi.org/10.1093/biomethods/bpae029openalex-snapshot

A highly sensitive stem-loop RT-qPCR method to study siRNA intracellular pharmacokinetics and pharmacodynamics

inferred← citeshttps://doi.org/10.1093/cvr/cvab100openalex-snapshot

Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics

inferred← citeshttps://doi.org/10.1093/nar/gkab718openalex-snapshot

Towards next generation antisense oligonucleotides: mesylphosphoramidate modification improves therapeutic index and duration of effect of gapmer antisense oligonucleotides

inferred← citeshttps://doi.org/10.1093/nar/gkac308openalex-snapshot

Targeted delivery to macrophages and dendritic cells by chemically modified mannose ligand-conjugated siRNA

inferred← citeshttps://doi.org/10.1093/nar/gkac456openalex-snapshot

Considerations and recommendations for assessment of plasma protein binding and drug–drug interactions for siRNA therapeutics

inferred← citeshttps://doi.org/10.1093/nar/gkad023openalex-snapshot

Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics

inferred← citeshttps://doi.org/10.1093/nar/gkad1148openalex-snapshot

Editorial: Nucleic Acids Research virtual issue dedicated to nucleic acid therapeutics, 2018–2023

inferred← citeshttps://doi.org/10.1093/nar/gkad268openalex-snapshot

Impact of stereopure chimeric backbone chemistries on the potency and durability of gene silencing by RNA interference

inferred← citeshttps://doi.org/10.1093/nar/gkae1195openalex-snapshot

High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination

inferred← citeshttps://doi.org/10.1093/nar/gkae350openalex-snapshot

Evaluating the oral delivery of GalNAc-conjugated siRNAs in rodents and non-human primates

inferred← citeshttps://doi.org/10.1093/nar/gkaf1063openalex-snapshot

Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia

inferred← citeshttps://doi.org/10.1093/nar/gkaf234openalex-snapshot

Next generation APOBEC3 inhibitors: optimally designed for potency and nuclease stability

inferred← citeshttps://doi.org/10.1093/nar/gkaf479openalex-snapshot

Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy

showing the first 200 of 283

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