ArticleProceedings of the National Academy of Sciences of the United States of America2012
Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2018Pooled it
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Reduced Muscle Force in Dystrophic DMDΔ52 Pigs Is Incompletely Restored by Systemic Transcript Reframing (DMDΔ51-52).Journal of cachexia, sarcopenia and muscle · 2025Article
- Exon-Skipping Using Antisense Oligonucleotides for Laminin-Alpha2-Deficient Muscular Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- In Vivo Evaluation of Single- and Multi-Exon-Skipping in mdx52 Mice.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Tips to Design Effective Splice-Switching Antisense Oligonucleotides for Exon Skipping and Exon Inclusion.Methods in molecular biology (Clifton, N.J.) · 2025Article
- In Vivo Evaluation of Multiple Exon Skipping with Peptide-PMOs in Cardiac and Skeletal Muscles in Dystrophic Dogs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Deletion of exons 45 to 55 in the DMD gene: from the therapeutic perspective to the in vitro model.Skeletal muscle · 2024Article
- Networking to OptimizeBiomedicines · 2023Article
- Therapeutic approaches for Duchenne muscular dystrophy.Nature reviews. Drug discovery · 2023Review
- Dual CRISPR-Cas3 system for inducing multi-exon skipping in DMD patient-derived iPSCs.Stem cell reports · 2023Article
- Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy.Pharmaceutics · 2023Review
- Restoring Dystrophin Expression by Skipping Exons 6 and 8 in Neonatal Dystrophic Dogs.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Exons 45-55 Skipping Using Antisense Oligonucleotides in Immortalized Human DMD Muscle Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion.Annals of neurology · 2022Article
- In vivo restoration of dystrophin expression in mdx mice using intra-muscular and intra-arterial injections of hydrogel microsphere carriers of exon skipping antisense oligonucleotides.Cell death & disease · 2022Article
- Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Development of Therapeutic RNA Manipulation for Muscular Dystrophy.Frontiers in genome editing · 2022Review
- Animal models for researching approaches to therapy of Duchenne muscular dystrophy.Transgenic research · 2021Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 5 countries.
Funding
Abstract
Duchenne muscular dystrophy (DMD), the commonest form of muscular dystrophy, is caused by lack of dystrophin. One of the most promising therapeutic approaches is antisense-mediated elimination of frame-disrupting mutations by exon skipping. However, this approach faces two major hurdles: limited applicability of each individual target exon and uncertain function and stability of each resulting truncated dystrophin. Skipping of exons 45-55 at the mutation hotspot of the DMD gene would address both issues. Theoretically it could rescue more than 60% of patients with deletion mutations. Moreover, spontaneous deletions of this specific region are associated with asymptomatic or exceptionally mild phenotypes. However, such multiple exon skipping of exons 45-55 has proved technically challenging. We have therefore designed antisense oligo (AO) morpholino mixtures to minimize self- or heteroduplex formation. These were tested as conjugates with cell-penetrating moieties (vivo-morpholinos). We have tested the feasibility of skipping exons 45-55 in H2K-mdx52 myotubes and in mdx52 mice, which lack exon 52. Encouragingly, with mixtures of 10 AOs, we demonstrated skipping of all 10 exons in vitro, in H2K-mdx52 myotubes and on intramuscular injection into mdx52 mice. Moreover, in mdx52 mice in vivo, systemic injections of 10 AOs induced extensive dystrophin expression at the subsarcolemma in skeletal muscles throughout the body, producing up to 15% of wild-type dystrophin protein levels, accompanied by improved muscle strength and histopathology without any detectable toxicity. This is a unique successful demonstration of effective rescue by exon 45-55 skipping in a dystrophin-deficient animal model.
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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.