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- Title
Dystrophin delivery to muscles of mdx mice using lentiviral vectors leads to myogenic progenitor targeting and stable gene expression.
- Authors
Kimura, En; Li, Sheng; Gregorevic, Paul; Fall, Brent M; Chamberlain, Jeffrey S
- Abstract
To explore whether stable transduction of myogenic stem cells using lentiviral vectors could be of benefit for treating dystrophic muscles, we generated vectors expressing a functional microdystrophin/enhanced green fluorescence protein fusion (microDys/eGFP) gene. Lentiviral vector injection into neonatal mdx(4cv) muscles resulted in widespread and stable expression of dystrophin for at least 2 years. This expression resulted in a significant amelioration of muscle pathophysiology as assessed by a variety of histological and functional assays. To assess whether this long-term expression was accompanied by stable transduction of satellite cells, we harvested muscle mononuclear cells 1 year after vector injection. Up to 20% of the cultured myoblast colonies expressed the microDys/eGFP transgene following myotube formation. Furthermore, transplantation of the muscle mononuclear cells into secondary mdx(4cv) recipients showed their ability to regenerate dystrophin-expressing myofibers in vivo. The ability to isolate myogenic cells able to form dystrophin-positive myotubes or myofibers in vitro and in vivo >1 year postinjection indicates that the vectors stably transduced muscle satellite cells, or a progenitor of such cells, in neonatal mdx(4cv) muscles. These studies suggest that integrating lentiviral vectors have potential utility for gene therapy of muscular dystrophy.
- Publication
Molecular therapy : the journal of the American Society of Gene Therapy, 2010, Vol 18, Issue 1, p206
- ISSN
1525-0024
- Publication type
Journal Article
- DOI
10.1038/mt.2009.253