Abstract
DUCHENNE progressive muscular dystrophy is a lethal and common X-linked genetic disease1 caused by the absence of dystrophin2,3, a 427K protein encoded by a 14 kilobase transcript4. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors5–7, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin8. Adenovirus is an efficient vector for in vivo expression of various foreign genes9–13. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart12,13. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA14 driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse15,16, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
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Ragot, T., Vincent, N., Chafey, P. et al. Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. Nature 361, 647–650 (1993). https://doi.org/10.1038/361647a0
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DOI: https://doi.org/10.1038/361647a0
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