ArticleNucleic acids research2022
Control of backbone chemistry and chirality boost oligonucleotide splice switching activity.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- 5'-Palmitate Lipid and Internal LNA-Piperidyl Triesters Enhance the RNA Affinity and Activity of Splice-Switching Oligonucleotides.Journal of the American Chemical Society · 2026Article
- Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers.Pharmaceutics · 2026Review
- Antisense RNA therapies for muscular dystrophies.Journal of neuromuscular diseases · 2026Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Progress and prospects in antisense oligonucleotide-mediated exon skipping therapies for Duchenne muscular dystrophy.Journal of muscle research and cell motility · 2025Review
- Article
- Synthesis ofThe Journal of organic chemistry · 2025Article
- Amphiphilic Oligonucleotide Derivatives as a Tool to Study DNA Repair Proteins.International journal of molecular sciences · 2025Article
- Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Development of bioconjugate-based delivery systems for nucleic acids.RNA (New York, N.Y.) · 2024Review
- Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.Pharmaceutics · 2024Review
- Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model.Nature communications · 2024Article
- Rational design of base, sugar and backbone modifications improves ADAR-mediated RNA editing.Nucleic acids research · 2024Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutantMolecular therapy. Nucleic acids · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
42 authors at 2 institutions in 2 countries.
Funding
Abstract
Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations of existing technologies, we engineered chimeric stereopure oligonucleotides with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these chimeric stereopure oligonucleotides have markedly improved pharmacology and efficacy compared with PS-modified oligonucleotides, preventing premature death and improving median survival from 49 days to at least 280 days in a dystrophic mouse model with an aggressive phenotype. These data demonstrate that chemical optimization alone can profoundly impact oligonucleotide pharmacology and highlight the potential for continued innovation around the oligonucleotide backbone. More specifically, we conclude that chimeric stereopure oligonucleotides are a promising splice-switching modality with potential for the treatment of neuromuscular and other genetic diseases impacting difficult to reach tissues such as the skeletal muscle and heart.
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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 Socratic graph.