ArticleProceedings of the National Academy of Sciences of the United States of America2007
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers.
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Who cites it
224 citing papers in PubMed, 679 citations in OpenAlex.
- RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection.Hepatology (Baltimore, Md.) · 2020Trial
- Safety, Tolerability, and Pharmacokinetics of ARC-520 Injection, an RNA Interference-Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers.Clinical pharmacology in drug development · 2017Trial
- Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.International journal of pharmaceutics: X · 2026Review
- Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis.Nature communications · 2025Article
- Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects.JACC. Basic to translational science · 2025Article
- Recent Update on siRNA Therapeutics.International journal of molecular sciences · 2025Review
- RNA aptamer-mediated RNA nanotechnology for potential treatment of cardiopulmonary diseases.Pharmacological research · 2025Review
- Covalent Polymer-RNA Conjugates for Potent Activation of the RIG-I Pathway.Advanced healthcare materials · 2025Article
- Advanced siRNA delivery in combating hepatitis B virus: mechanistic insights and recent updates.Journal of nanobiotechnology · 2024Review
- Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.Cancer cell international · 2024Article
- Principle, application and challenges of development siRNA-based therapeutics against bacterial and viral infections: a comprehensive review.Frontiers in microbiology · 2024Review
- Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment.Drug delivery · 2023Review
- Multivalent Targeting of the Asialoglycoprotein Receptor by Virus-Like Particles.Small (Weinheim an der Bergstrasse, Germany) · 2023Article
- Delivery of gene editing therapeutics.Nanomedicine : nanotechnology, biology, and medicine · 2023Review
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking.Cells · 2023Review
- Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.Cell communication and signaling : CCS · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Progress on siRNA-based gene therapy targeting secondary injury after intracerebral hemorrhage.Gene therapy · 2023Review
164 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Achieving efficient in vivo delivery of siRNA to the appropriate target cell would be a major advance in the use of RNAi in gene function studies and as a therapeutic modality. Hepatocytes, the key parenchymal cells of the liver, are a particularly attractive target cell type for siRNA delivery given their central role in several infectious and metabolic disorders. We have developed a vehicle for the delivery of siRNA to hepatocytes both in vitro and in vivo, which we have named siRNA Dynamic PolyConjugates. Key features of the Dynamic PolyConjugate technology include a membrane-active polymer, the ability to reversibly mask the activity of this polymer until it reaches the acidic environment of endosomes, and the ability to target this modified polymer and its siRNA cargo specifically to hepatocytes in vivo after simple, low-pressure i.v. injection. Using this delivery technology, we demonstrate effective knockdown of two endogenous genes in mouse liver: apolipoprotein B (apoB) and peroxisome proliferator-activated receptor alpha (ppara). Knockdown of apoB resulted in clear phenotypic changes that included a significant reduction in serum cholesterol and increased fat accumulation in the liver, consistent with the known functions of apoB. Knockdown of ppara also resulted in a phenotype consistent with its known function, although with less penetrance than observed in apoB knockdown mice. Analyses of serum liver enzyme and cytokine levels in treated mice indicated that the siRNA Dynamic PolyConjugate was nontoxic and well tolerated.
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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.