Dystrophin delivery to muscles of mdx mice using lentiviral vectors leads to myogenic progenitor targeting and stable gene expression

En Kimura, Sheng Li, Paul Gregorevic, Brent M. Fall, Jeffrey S Chamberlain

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40 Citations (Scopus)


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 (νDys/eGFP) gene. Lentiviral vector injection into neonatal mdx4cv 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 μDys/eGFP transgene following myotube formation. Furthermore, transplantation of the muscle mononuclear cells into secondary mdx4cv 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 mdx4cv muscles. These studies suggest that integrating lentiviral vectors have potential utility for gene therapy of muscular dystrophy.

Original languageEnglish
Pages (from-to)206-213
Number of pages8
JournalMolecular Therapy
Issue number1
Publication statusPublished - Jan 2010
Externally publishedYes

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