ArticleNucleic acids research2013
The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 51 citations in OpenAlex.
- Lipid nanoparticle delivery of antisense gapmers attenuates pathology in a mouse model of facioscapulohumeral muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA.Molecules (Basel, Switzerland) · 2024Review
- 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
- Article
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- Innovative developments and emerging technologies in RNA therapeutics.RNA biology · 2022Article
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Selective tissue targeting of synthetic nucleic acid drugs.The Journal of clinical investigation · 2019Review
- Retro-1-Oligonucleotide Conjugates. Synthesis and Biological Evaluation.Molecules (Basel, Switzerland) · 2019Article
- Intracellular Trafficking and Endosomal Release of Oligonucleotides: What We Know and What We Don't.Nucleic acid therapeutics · 2018Review
- Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs.Nucleic acid therapeutics · 2018Review
- Ammonium and arsenic trioxide are potent facilitators of oligonucleotide function when delivered by gymnosis.Nucleic acids research · 2018Article
- Structure-activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides.Nucleic acids research · 2018Article
- A Novel Family of Small Molecules that Enhance the Intracellular Delivery and Pharmacological Effectiveness of Antisense and Splice Switching Oligonucleotides.ACS chemical biology · 2017Article
- Intra-endosomal trafficking mediated by lysobisphosphatidic acid contributes to intracellular release of phosphorothioate-modified antisense oligonucleotides.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The attainment of strong pharmacological effects with oligonucleotides is hampered by inefficient access of these molecules to their sites of action in the cytosol or nucleus. Attempts to address this problem with lipid or polymeric delivery systems have been only partially successful. Here, we describe a novel alternative approach involving the use of a non-toxic small molecule to enhance the pharmacological effects of oligonucleotides. The compound Retro-1 was discovered in a screen for small molecules that reduce the actions of bacterial toxins and has been shown to block the retrograde trafficking pathway. We demonstrate that Retro-1 can also substantially enhance the effectiveness of antisense and splice switching oligonucleotides in cell culture. This effect occurs at the level of intracellular trafficking or processing and is correlated with increased oligonucleotide accumulation in the nucleus but does not involve the perturbation of lysosomal compartments. We also show that Retro-1 can alter the effectiveness of splice switching oligonucleotides in the in vivo setting. These observations indicate that it is possible to enhance the pharmacological actions of oligonucleotides using non-toxic and non-lysosomotropic small molecule adjuncts.
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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.