ArticleMolecular therapy. Methods & clinical development2015
Short-lived recombinant adeno-associated virus transgene expression in dystrophic muscle is associated with oxidative damage to transgene mRNA.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Timing matters: Exon skipping therapy is most effective when initiated early in a mouse model of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2026Article
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Lifelong Outcomes of Systemic Adeno-Associated Virus Micro-Dystrophin Gene Therapy in a Murine Duchenne Muscular Dystrophy Model.Human gene therapy · 2023Article
- Duchenne muscular dystrophy: disease mechanism and therapeutic strategies.Frontiers in physiology · 2023Review
- Muscle regeneration affects Adeno Associated Virus 1 mediated transgene transcription.Scientific reports · 2022Article
- Exon-Skipping in Duchenne Muscular Dystrophy.Journal of neuromuscular diseases · 2021Review
- Effective restoration of dystrophin expression in iPSCComputational and structural biotechnology journal · 2020Article
- Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- [A review of gene therapy for Duchenne muscular dystrophy].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
- Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies.Oxidative medicine and cellular longevity · 2016Review
- Perspective on Adeno-Associated Virus Capsid Modification for Duchenne Muscular Dystrophy Gene Therapy.Human gene therapy · 2015Review
- The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.Current gene therapy · 2015Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical gene therapy strategies using recombinant adeno-associated virus (AAV) vectors in animal models of Duchenne muscular dystrophy have shown dramatic phenotype improvements, but long-lasting efficacy remains questionable. It is believed that in dystrophic muscles, transgene persistence is hampered, notably by the progressive loss of therapeutic vector genomes resulting from muscle fibers degeneration. Intracellular metabolic perturbations resulting from dystrophin deficiency could also be additional factors impacting on rAAV genomes and transgene mRNA molecular fate. In this study, we showed that rAAV genome loss is not the only cause of reduced transgene mRNA level and we assessed the contribution of transcriptional and post-transcriptional factors. We ruled out the implication of transgene silencing by epigenetic mechanisms and demonstrated that rAAV inhibition occurred mostly at the post-transcriptional level. Since Duchenne muscular dystrophy (DMD) physiopathology involves an elevated oxidative stress, we hypothesized that in dystrophic muscles, transgene mRNA could be damaged by oxidative stress. In the mouse and dog dystrophic models, we found that rAAV-derived mRNA oxidation was increased. Interestingly, when a high expression level of a therapeutic transgene is achieved, oxidation is less pronounced. These findings provide new insights into rAAV transductions in dystrophic muscles, which ultimately may help in the design of more effective clinical trials.
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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.