Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice

Abstract

DUCHENNE progressive muscular dystrophy is a lethal and common X-linked genetic disease¹ caused by the absence of dystrophin^2,3, 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 donors^5–7, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin⁸. Adenovirus is an efficient vector for in vivo expression of various foreign genes^9–13. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart^12,13. 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 mouse^15,16, 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.