Journal article
Dystrophin delivery to muscles of mdx mice using lentiviral vectors leads to myogenic progenitor targeting and stable gene expression
E Kimura, S Li, P Gregorevic, BM Fall, JS Chamberlain
Molecular Therapy | CELL PRESS | Published : 2010
DOI: 10.1038/mt.2009.253
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 (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 v..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Arthur Thompson for reviewing this manuscript and Laura Stewart for her help with the Bethesda assay. We are grateful to Rita Sarker for providing the hemophilic mice. We also thank Baxter Biosciences for providing the rhFVIII (Advate). This work was supported by grant funding from the Hemophilia Association of New York and a Judith Graham Pool Postdoctoral Fellowship award to Rui-Jun Su. The authors have no competing financial interests. R. S. designed and performed research, analyzed data, and wrote the manuscript. A. E. performed research. Y. L. designed research and analyzed data. D. B. analyzed data. S. W. P. provided reagents and designed research. N. C. J. designed research, analyzed data, and wrote the manuscript.