ArticleNucleic acids research2015
Identification of siRNA delivery enhancers by a chemical library screen.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 69 citations in OpenAlex.
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- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- Toward understanding lipid reorganization in RNA lipid nanoparticles in acidic environments.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs.Communications biology · 2024Review
- LDLR-Mediated Targeting and Productive Uptake of siRNA-Peptide Ligand Conjugates In Vitro and In Vivo.Pharmaceutics · 2024Article
- An Endosomal Escape Trojan Horse Platform to Improve Cytosolic Delivery of Nucleic Acids.ACS nano · 2024Article
- Antitumor effects of chemically modified miR-143 lipoplexes in a mouse model of pelvic colorectal cancer via myristoylated alanine-rich C kinase substrate downregulation.Molecular therapy. Nucleic acids · 2023Article
- Nucleic acid amphiphiles: Synthesis, properties, and applications.Molecular therapy. Nucleic acids · 2023Review
- Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking.Cells · 2023Review
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- Article
- Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers.Frontiers in chemistry · 2021Review
- Transport Oligonucleotides-A Novel System for Intracellular Delivery of Antisense Therapeutics.Molecules (Basel, Switzerland) · 2020Article
- DNA unchained: two assays to discover and study inhibitors of the DNA clustering function of barrier-to-autointegration factor.Scientific reports · 2020Article
- Arrayed CRISPR Screening Identifies Novel Targets That Enhance the Productive Delivery of mRNA by MC3-Based Lipid Nanoparticles.SLAS discovery : advancing life sciences R & D · 2020Article
- Imaging small molecule-induced endosomal escape of siRNA.Nature communications · 2020Article
- Nanomolar-potency 'co-potentiator' therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most delivery systems for small interfering RNA therapeutics depend on endocytosis and release from endo-lysosomal compartments. One approach to improve delivery is to identify small molecules enhancing these steps. It is unclear to what extent such enhancers can be universally applied to different delivery systems and cell types. Here, we performed a compound library screen on two well-established siRNA delivery systems, lipid nanoparticles and cholesterol conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2-5 fold. Strikingly, most enhancers displayed specificity for one delivery system only. By a combination of quantitative fluorescence and electron microscopy we found that the enhancers substantially differed in their mechanism of action, increasing either endocytic uptake or release of siRNAs from endosomes. Furthermore, they acted either on the delivery system itself or the cell, by modulating the endocytic system via distinct mechanisms. Interestingly, several compounds displayed activity on different cell types. As proof of principle, we showed that one compound enhanced siRNA delivery in primary endothelial cells in vitro and in the endocardium in the mouse heart. This study suggests that a pharmacological approach can improve the delivery of siRNAs in a system-specific fashion, by exploiting distinct mechanisms and acting upon multiple cell types.
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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.