ArticleHuman gene therapy2011
Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice.
Article in Human gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Enhanced therapeutic potential of a microdystrophin with an extended C-terminal domain.Molecular therapy. Methods & clinical development · 2025Article
- Long-Term Dystrophin Replacement Therapy in Duchenne Muscular Dystrophy Causes Cardiac Inflammation.JACC. Basic to translational science · 2025Article
- The road toward AAV-mediated gene therapy of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- In Silico Structural Prediction for the Generation of Novel Performant Midi-Dystrophins Based on Intein-Mediated Dual AAV Approach.International journal of molecular sciences · 2024Article
- Assessment of Therapeutic Potential of a Dual AAV Approach for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2023Article
- Microdystrophin Gene Addition Significantly Improves Muscle Functionality and Diaphragm Muscle Histopathology in a Fibrotic Mouse Model of Duchenne Muscular Dystrophy.International journal of molecular sciences · 2023Article
- Gene Therapy for Regenerative Medicine.Pharmaceutics · 2023Review
- Duchenne muscular dystrophy: disease mechanism and therapeutic strategies.Frontiers in physiology · 2023Review
- Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDGene therapy · 2022Article
- TRPC3, but not TRPC1, as a good therapeutic target for standalone or complementary treatment of DMD.Journal of translational medicine · 2021Article
- Review
- Next-generation muscle-directed gene therapy by in silico vector design.Nature communications · 2019Article
- Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- Single Intramuscular Injection of AAV-shRNA Reduces DNM2 and Prevents Myotubular Myopathy in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Dual AAV Gene Therapy for Duchenne Muscular Dystrophy with a 7-kb Mini-Dystrophin Gene in the Canine Model.Human gene therapy · 2018Article
- Nanotherapy for Duchenne muscular dystrophy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018Review
- Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy.Nature communications · 2017Article
- piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts.Nucleic acids research · 2016Article
- Full-length Dysferlin Transfer by the Hyperactive Sleeping Beauty Transposase Restores Dysferlin-deficient Muscle.Molecular therapy. Nucleic acids · 2016Article
- Advances in gene therapy for muscular dystrophies.F1000Research · 2016Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed. We have previously shown the efficiency of mRNA sequence-optimized microdystrophin (ΔR4-23/ΔCT, called MD1) with deletion of spectrin-like repeat domain 4 to 23 and CT domain in ameliorating the pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signaling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain-extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction-induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy.
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