ArticleBioconjugate chemistry2018
Novel Cluster and Monomer-Based GalNAc Structures Induce Effective Uptake of siRNAs in Vitro and in Vivo.
Article in Bioconjugate chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Exosome Nanotechnology in Molecular Medicine Advances, Applications and Challenges in Gene Therapy.Expert reviews in molecular medicine · 2026Review
- Novel diamine-scaffold basedRSC advances · 2024Article
- A combinatorial approach for achieving CNS-selective RNAi.Nucleic acids research · 2024Article
- Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure.Science advances · 2024Article
- Silencing Apoe with divalent-siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.Nucleic acids research · 2024Article
- Triazole-linked Nucleic Acids: Synthesis, Therapeutics and Synthetic Biology Applications.Current organic synthesis · 2024Review
- Astrocyte-targeted siRNA delivery by adenosine-functionalized LNP in mouse TBI model.Molecular therapy. Nucleic acids · 2023Article
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Ratiometric, pH-Sensitive Probe for Monitoring siRNA Delivery.Journal of the American Chemical Society · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- PK-modifying anchors significantly alter clearance kinetics, tissue distribution, and efficacy of therapeutics siRNAs.Molecular therapy. Nucleic acids · 2022Article
- Targeted delivery to macrophages and dendritic cells by chemically modified mannose ligand-conjugated siRNA.Nucleic acids research · 2022Article
- Evolution of complexity in non-viral oligonucleotide delivery systems: from gymnotic delivery through bioconjugates to biomimetic nanoparticles.RNA biology · 2022Review
- Review
- Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs.Pharmaceutics · 2021Review
- Synthesis of GalNAc-Oligonucleotide Conjugates Using GalNAc Phosphoramidite and Triple-GalNAc CPG Solid Support.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Less Is More: Novel Hepatocyte-Targeted siRNA Conjugates for Treatment of Liver-Related Disorders.Molecular therapy. Nucleic acids · 2020Article
- A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics.Nucleic acids research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
GalNAc conjugation is emerging as a dominant strategy for delivery of therapeutic oligonucleotides to hepatocytes. The structure and valency of the GalNAc ligand contributes to the potency of the conjugates. Here we present a panel of multivalent GalNAc variants using two different synthetic strategies. Specifically, we present a novel conjugate based on a support-bound trivalent GalNAc cluster, and four others using a GalNAc phosphoramidite monomer that was readily assembled into tri- or tetravalent designs during solid phase oligonucleotide synthesis. We compared these compounds to a clinically used trivalent GalNAc cluster both in vitro and in vivo. In vitro, cluster-based and phosphoramidite-based scaffolds show a similar rate of internalization in primary hepatocytes, with membrane binding observed as early as 5 min. All tested compounds provided potent, dose-dependent silencing, with 2-4% of injected dose recoverable from liver after 1 week. The two preassembled trivalent GalNAc clusters showed higher tissue accumulation and gene silencing relative to di-, tri-, or tetravalent GalNAc conjugates assembled via phosphoramidite chemistry.
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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.