Molecular biological study to establish the treatment for Duchenne muscular dystrophy

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Duchenne muscular dystrophy (DMD) is a rapid progressive disease which usually results in death at around the age of 20, while Becker muscular dystrophy (BMD) is a clinically less severe form of the disease which often has only slight debilitating effects. DMD and BMD are allelic diseases caused by mutations of the dystrophin gene, which consists of 79 exons. Deletion mutations have been identified in two thirds of DMD/BMD cases, and the clinical progression of DMD or BMD patients can be predicted from whether or not the deletion maintains or disrupts the translational reading frame of the mRNA.Gene therapy is attracting increasing attention as a plausible treatment for DMD.And reading frame displacement to correct the effects of frame-shift deletions on translation is one of approaches.In this study we first report that exon skipping from the dystrophin gene transcript could in living cells by an antisense oligodeoxynucleotide (ODN) complementary to an exon recognition sequence (ERS). Incubation of lymphoblastoid cells with an antisense ODN against the purine-rich region of dystrophin exon 19 resulted in skipping of the exon from the dystrophin transcript. Skipping of exon 19 started to appear after 6 hours of incubation, and complete skipping was observed after 24 hours of incubation. None of the other 78 dystrophin exons were skipped, and exon 19 skipping could not be induced by the sense ODN or by an antisense ODN corresponding to another ERS.These results showed that antisense ODN against ERS induces exon skipping even in living cells. This paved the road to establish gene therapy for DMD.