Effective restoration of dystrophin-associated proteins in vivo by adenovirus-mediated transfer of truncated dystrophin cDNAs

A series of truncated dystrophin cDNAs (3.1-4.2 kbp) containing only three, three, two or one rod repeats with hinge 1 and 4 (named Delta DysAX2, AX11, AH3, M3, respectively) or no rod repeat retaining either hinge 1 or 4 (named Delta DysH1, H4, respectively) were constructed, These cDNAs were introduced into skeletal muscle of adult mdx mice using the adenovirus vector with a strong CAG promoter. Delta DysAX2, AX11, AH3 and Delta DysM3 expressed themselves successfully and recovered dystrophin-associated proteins effectively. Especially 3.7 kbp cDNA for Delta DysM3 offers the possibility of an approach utilizing newly developed virus vectors, such as an adeno-associated virus vector, toward gene therapy of Duchenne muscular dystrophy. (C) 1998 Federation of European Biochemical Societies.