ArticleThe American journal of pathology2012
Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis.Scientific reports · 2018Pooled it
- Molecular Bases of Myopathies and Their Impact on Clinical Practice: Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Spatiotemporal analysis of dystrophin expression during muscle repair.Skeletal muscle · 2025Article
- Enhanced therapeutic potential of a microdystrophin with an extended C-terminal domain.Molecular therapy. Methods & clinical development · 2025Article
- Targeting Drug Delivery System to Skeletal Muscles: A Comprehensive Review of Different Approaches.Journal of cachexia, sarcopenia and muscle · 2025Review
- In Vivo Evaluation of Dystrophin Exon Skipping in mdx Mice.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Nanocarriers: Exploring the Potential of Oligonucleotide Delivery.Current drug delivery · 2025Review
- Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Systemic PPMO-mediated dystrophin expression in the Dup2 mouse model of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2022Article
- A cell-penetrating peptide enhances delivery and efficacy of phosphorodiamidate morpholino oligomers inMolecular therapy. Nucleic acids · 2022Article
- Non-uniform dystrophin re-expression after CRISPR-mediated exon excision in the dystrophin/utrophin double-knockout mouse model of DMD.Molecular therapy. Nucleic acids · 2022Article
- Considerations for Generating Humanized Mouse Models to Test Efficacy of Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids.International journal of molecular sciences · 2021Article
- Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy.Gene therapy · 2020Review
- Triazine-cored polymeric vectors for antisense oligonucleotide delivery in vitro and in vivo.Journal of nanobiotechnology · 2020Article
- Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice.The Journal of clinical investigation · 2019Article
- Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases.EBioMedicine · 2019Review
- Aminoglycoside Enhances the Delivery of Antisense Morpholino Oligonucleotides In Vitro and in mdx Mice.Molecular therapy. Nucleic acids · 2019Article
- Antisense oligonucleotides for the treatment of cardiomyopathy in Duchenne muscular dystrophy.American journal of translational research · 2019Review
- Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges.Journal of personalized medicine · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model.
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