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Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD)

Gene Therapy volume 11, pages S109–S121 (2004)Cite this article

Abstract

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder caused by recessive mutations in the dystrophin gene. The size of the gene (2.4 Mb) and mRNA (14 kb) in addition to immunogenicity problems and inefficient transduction of mature myofibres by currently available vector systems are formidable obstacles to the development of efficient gene therapy approaches. Adeno-associated viral (AAV) vectors overcome many of the problems associated with other vector systems (nonpathogenicity and minimal immunogenicity, extensive cell and tissue tropism) but accommodate limited transgene capacity (<5 kb). As a result of these observations, a number of laboratories worldwide have engineered a series of microdystrophin cDNAs based on genotype–phenotype relationship in Duchenne (DMD) and Becker (BMD) dystrophic patients, and transgenic studies in mdx mice. Recent progress in characterization of AAV serotypes from various species has demonstrated that alternative AAV serotypes are far more efficient in transducing muscle than the traditionally used AAV2. This article summarizes the current progress in the field of recombinant adeno-associated viral (rAAV) delivery for DMD, including optimization of recombinant AAV-microdystrophin vector systems/cassettes targeting the skeletal and cardiac musculature.

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Acknowledgements

The authors would like to thank the Muscular Dystrophy Campaign (MDC), UK and the Association Francaise Contres les Myopathies (AFM) for funding and support. We also thank J Harris for critically reviewing this manuscript and M Mezzina for the invitation to contribute.

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  1. Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK

    T Athanasopoulos, IR Graham, H Foster & G Dickson

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  1. T Athanasopoulos
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Athanasopoulos, T., Graham, I., Foster, H. et al. Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD). Gene Ther 11 (Suppl 1), S109–S121 (2004). https://doi.org/10.1038/sj.gt.3302379

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