Journal article

Gene Therapy of mdx Mice With Large Truncated Dystrophins Generated by Recombination Using rAAV6

Guy L Odom, Paul Gregorevic, James M Allen, Jeffrey S Chamberlain

MOLECULAR THERAPY | CELL PRESS | Published : 2011

Abstract

Recombinant adeno-associated viral (rAAV) vector-mediated gene transfer represents a promising approach for many diseases. However, the applicability of rAAV vectors has long been hindered by the small (~4.8 kb) DNA packaging capacity. This limitation can hamper the packaging and delivery of critical regulatory elements and/or larger coding sequences, such as the ~14-kb dystrophin complementary DNA (cDNA) that is of interest for gene therapy of Duchenne muscular dystrophy (DMD). Here, we have demonstrated reconstitution of an expression cassette (7.3 kb) encoding a highly functional "minidystrophin" protein (ΔH2-R19, 222 kd) in vivo following intravascular co-delivery of two independent rAAV..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

This work was supported by grants from the National Institutes of Health (AR40864 and AG033610 to J.S.C.). G.L.O. was supported by a National Institutes of Health National Research Service Award (T32 HL07828) and a Development Grant from the Muscular Dystrophy Association (USA). P.G. was supported by a Development Grant from the Muscular Dystrophy Association (USA).