Journal article
In vivo muscle gene transfer of full-length dystrophin with an adenoviral vector that lacks all viral genes
Gene therapy, Vol.3(11), pp.965-972
1996
PMID: 8940636
Abstract
Duchenne muscular dystrophy (DMD) is an important target for gene transfer because of the disease's high frequency and devastating course. To date, adenoviral vector-mediated gene transfer for DMD has been unavailable because (1) adenoviral vectors were unable to accommodate the full-length dystrophin cDNA (14 kb); and (2) adenoviral vectors induced inflammatory reactions in the gene transfer recipient. We addressed both problems with a novel adenoviral vector that contains no viral genes and encodes 28.2 kb of foreign DNA including both the full-length dystrophin cDNA with the muscle creatine kinase promoter for transcriptional control and a lacZ marker gene. This report presents the in vivo expression of dystrophin and β-galactosidase from this vector in skeletal muscle of the mdx mouse, a mutant mouse that lacks dystrophin. Somatic delivery of the vector by intramuscular injection in 6-day-old mice resulted in the expression of full-length, recombinant dystrophin at the muscle membrane. Dystrophin-associated proteins were restored in muscle fibers expressing recombinant dystrophin. Mdx muscle injected with our vector showed a decrease in the proportion of fibers with nuclei located centrally; centrally placed nuclei in muscle fibers are characteristic of cycles of degeneration and regeneration suffered by dystrophin-deficient muscle tissue. These results are strong evidence that adenoviral vector-mediated full-length dystrophin delivery provides substantial somatic function.
Details
- Title: Subtitle
- In vivo muscle gene transfer of full-length dystrophin with an adenoviral vector that lacks all viral genes
- Creators
- P. R CLEMENS - Department of Neurology, University of Pittsburgh, PA, United StatesS KOCHANEK - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesY SUNADA - Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United StatesS CHAN - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesH.-H CHEN - Department of Neurology, University of Pittsburgh, PA, United StatesK. P CAMPBELL - Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United StatesC. T CASKEY - Merck Research Laboratories, West Point, PA, United States
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.3(11), pp.965-972
- Publisher
- Nature Publishing Group; Basingstoke
- PMID
- 8940636
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Language
- English
- Date published
- 1996
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068371102771
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