ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
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- A New Option for the Management of Dyslipidemias: Advances in Research on the Small Interfering RNA Drug Inclisiran.Reviews in cardiovascular medicine · 2026Review
- Real-World Efficacy of Inclisiran in Veneto Region (Italy): The INCLIVEN Multicenter Registry.Cardiovascular drugs and therapy · 2026 · on this mapObservational
- Preclinical evaluation of gefitinib and betulin-loaded surface functionalized liposomes for the treatment of hepatocellular carcinoma via asialoglycoprotein receptor targeting.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Beyond inflammation: siRNA strategies for precision targeting in rheumatological disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- GalNAc-conjugated siRNA targeting C/EBPβ reverses metabolic dysfunction and restores liver homeostasis in a murine MASLD model.Molecular therapy. Nucleic acids · 2026Article
- Hepatocyte-Targeted Drug Delivery Strategies for Chronic Hepatitis B: Overcoming Delivery Barriers Toward Functional Cure.Pharmaceutics · 2026Review
- Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.Clinical pharmacokinetics · 2026Article
- Drug Delivery Systems for Hepatocellular Carcinoma: Bridging Pathophysiological Barriers and Advanced Nanomedicine Strategies.Drug design, development and therapy · 2026Review
- Lepodisiran: Effects on Lipoprotein(a) and Cardiovascular Outcomes in Adults with Elevated Lp(a).Cardiovascular & hematological disorders drug targets · 2026Review
- C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Intracellular fatty acid levels differentially impact target silencing by FDA-approved siRNA drugs.Biochemical pharmacology · 2025Article
- Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025Review
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5 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatocyte-specific asialoglycoprotein receptor (ASGPR) is an ideal candidate for targeted drug delivery to the liver due to its high capacity for substrate clearance from circulation together with its well-conserved expression and function across species. The development of GalNAc-siRNA conjugates, in which a synthetic triantennary N-acetylgalactosamine-based ligand is conjugated to chemically modified siRNA, has enabled efficient, ASGPR-mediated delivery to hepatocytes. To investigate the potential impact of variations in receptor expression on the efficiency of GalNAc-siRNA conjugate delivery, we evaluated the pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates in multiple pre-clinical models with reduced receptor expression. Despite greater than 50% reduction in ASGPR levels, GalNAc conjugate activity was retained, suggesting that the remaining receptor capacity was sufficient to mediate efficient uptake of potent GalNAc-siRNAs at pharmacologically relevant dose levels. Collectively, our data support a broad application of the GalNAc-siRNA technology for hepatic targeting, including disease states where ASGPR expression may be reduced.
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