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Systemic Gene Delivery for Muscle Gene Therapy

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Muscle Gene Therapy

Abstract

The muscular dystrophies (MDs) are a heterogeneous group of monogenetic disorders that affect striated muscles, often throughout the body. A promising approach to treating the MDs is to use gene therapy to replace, repair, or modify expression of the mutant gene. Accomplishing such a goal requires that gene expression cassettes, which comprise a gene regulatory element driving expression of an effecter DNA sequence and are followed by a transcriptional terminator, be delivered to target cells to counteract the effects of the mutation. For the MDs, this type of therapy will require delivering expression cassettes to all the striated muscles in a patient’s body. Striated muscle forms a significant percentage of total body mass, so the prospects for achieving such large spread delivery had seemed like a remote goal. Recent studies using a variety of vector systems indicate that genes can be delivered to muscles body wide by infusing them into the blood stream under appropriate conditions. The simplest and one of the most promising methods for systemic delivery involves infusion of vectors derived from adeno-associated virus (AAV). These recombinant AAV vectors can target muscles throughout the body of small, adult mammals and may be adaptable to larger animals and humans. Consequently, the use of rAAV vectors has great potential to lead to a therapy for the MDs and other disorders of striated muscle.

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Acknowledgments

This work was supported by grants R37AR040864 and U54HD047175 from the National Institutes for Health and by the Muscular Dystrophy Association (USA). We thank Brian Schultz for helpful suggestions and artwork.

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  1. Department of Neurology, Department of Medicine, and Department of Biochemistry, University of Washington, Seattle, WA, 98195-7720, USA

    Jeffrey S. Chamberlain

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  1. Dilip Garikipati
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  2. Jeffrey S. Chamberlain
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Correspondence to Jeffrey S. Chamberlain .

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  1. Molecular Microbiology & Immunology, University of Missouri, Hospital Dr. 1, Columbia, 65212, U.S.A.

    Dongsheng Duan

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Garikipati, D., Chamberlain, J.S. (2010). Systemic Gene Delivery for Muscle Gene Therapy. In: Duan, D. (eds) Muscle Gene Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1207-7_10

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