Journal article
Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy
Nature medicine, Vol.8(3), pp.253-261
03/2002
DOI: 10.1038/nm0302-253
PMID: 11875496
Abstract
Attempts to develop gene therapy for Duchenne muscular dystrophy (DMD) have been complicated by the enormous size of the dystrophin gene. We have performed a detailed functional analysis of dystrophin structural domains and show that multiple regions of the protein can be deleted in various combinations to generate highly functional mini- and micro-dystrophins. Studies in transgenic mdx mice, a model for DMD, reveal that a wide variety of functional characteristics of dystrophy are prevented by some of these truncated dystrophins. Muscles expressing the smallest dystrophins are fully protected against damage caused by muscle activity and are not morphologically different from normal muscle. Moreover, injection of adeno-associated viruses carrying micro-dystrophins into dystrophic muscles of immunocompetent mdx mice results in a striking reversal of histopathological features of this disease. These results demonstrate that the dystrophic pathology can be both prevented and reversed by gene therapy using micro-dystrophins.
Details
- Title: Subtitle
- Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy
- Creators
- Jeffrey S Chamberlain - University of WashingtonScott Q Harper - University of WashingtonMichael A Hauser - Duke UniversityChristiana DelloRusso - University of WashingtonDongsheng Duan - University of IowaRobert W Crawford - University of WashingtonStephanie F Phelps - University of Michigan–Ann ArborHollie A Harper - University of WashingtonAnn S Robinson - University of Michigan–Ann ArborJohn F Engelhardt - University of IowaSusan V Brooks - University of Michigan–Ann Arbor
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.8(3), pp.253-261
- DOI
- 10.1038/nm0302-253
- PMID
- 11875496
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Language
- English
- Date published
- 03/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284325302771
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