Journal article

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

MOLECULAR THERAPY | CELL PRESS | Published : 2010

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 a..

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University of Melbourne Researchers

Grants

Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Awarded by NATIONAL INSTITUTE ON AGING


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.