ArticleNucleic acids research2020
Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
165 citing papers in PubMed, 3 syntheses or guidelines pooled it, 267 citations in OpenAlex.
- Dissolving microneedles for nucleic acid delivery: A systematic search, review, and data synthesis.Acta biomaterialia · 2025Pooled it
- Model-based meta-analysis to quantify the effects of short interfering RNA therapeutics on hepatitis B surface antigen turnover in hepatitis B-infected mice.CPT: pharmacometrics & systems pharmacology · 2024Pooled it
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Decoding miRNA‑146a: Mechanisms of action in cardiovascular diseases and endocrine metabolic disorders (Review).International journal of molecular medicine · 2026Review
- A Dual-Halogen Labeling Strategy to Detect and Quantify Double-Stranded RNAs Using NanoSIMS: A Proof-of-Concept Study.ACS omega · 2026Article
- Zilebesiran, a Small Interfering RNA Therapeutic Targeting Angiotensinogen: Mechanism, Clinical Evidence, Safety, and Implementation Considerations.Life (Basel, Switzerland) · 2026Review
- Stimulus-Responsive Polymeric Carriers for Gene Delivery: Balancing Endosomal Escape with Nucleic Acid Release.Pharmaceutical research · 2026Review
- Pharmacokinetic/Pharmacodynamic Translation and Model-Informed Drug Development for Oligonucleotide Therapeutics.Journal of clinical pharmacology · 2026Review
- Review
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Smart Nanomaterials and Natural Biologics for Innate-Adaptive Immune Reprogramming: A Nanobiotechnology Framework for Translational Medicine.Nanomaterials (Basel, Switzerland) · 2026Review
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Therapeutic siRNA: Mechanisms, challenges, strategies, and clinical translation.Chinese medical journal · 2026Review
- Research progress and development strategies of antibody-oligonucleotide conjugates.Gene therapy · 2026Review
- RNA-Loaded Nanoparticles for Targeted Lung Delivery.Biomedicines · 2026Review
- Ionizable Polymeric Micelles Targeting Transferrin Receptor 1 Enhance Systemic mRNA Delivery to the Brain.Molecular pharmaceutics · 2026Article
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- [Anti-inflammatory effects of cell membrane vesicle-mediated delivery of small interfering RNA targeting tumor necrosis factor-α on dental pulp stem cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Engineered Akkermansia muciniphila vesicles for targeted pyroptosis and trained immunity to enhance immunotherapy in hepatocellular carcinoma.Cell reports. Medicine · 2026Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 2 institutions in 1 country.
Funding
Abstract
One hallmark of trivalent N-acetylgalactosamine (GalNAc)-conjugated siRNAs is the remarkable durability of silencing that can persist for months in preclinical species and humans. Here, we investigated the underlying biology supporting this extended duration of pharmacological activity. We found that siRNA accumulation and stability in acidic intracellular compartments is critical for long-term activity. We show that functional siRNA can be liberated from these compartments and loaded into newly generated Argonaute 2 protein complexes weeks after dosing, enabling continuous RNAi activity over time. Identical siRNAs delivered in lipid nanoparticles or as GalNAc conjugates were dose-adjusted to achieve similar knockdown, but only GalNAc-siRNAs supported an extended duration of activity, illustrating the importance of receptor-mediated siRNA trafficking in the process. Taken together, we provide several lines of evidence that acidic intracellular compartments serve as a long-term depot for GalNAc-siRNA conjugates and are the major contributor to the extended duration of activity observed in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.