THE PRINCIPLES OF GENE-THERAPY IN DUCHENNE MUSCULAR-DYSTROPHY

Somatic cell gene therapy (GT) for genetic disease such as Duchenne mu scular dystrophy entails the introduction of normal, or at least funct ionally adequate, alleles of a gene into target cells for correction o r mitigation of deleterious consequences of the disease's characterist ic mutation. The following factors have a major impact upon the effici ency of GT: the artificial gene construct, the promoter, the delivery system, and the mode of dissemination of the therapeutic genes. For sk eletal muscles, replication-defective adenovirus represents an efficie nt delivery system, but only if immature muscle cells are abundant in the muscle. The major drawback of adenoviruses is that the maximal ins ert, capacity is only about 7.5 kb, which is only sufficient to accomm odate a dystrophin minigene (6.3 kb) with a constitutive promoter. The se and many other problems still require solution in experimental anim als before single-muscle pilot studies of GT can be undertaken for suc h human muscle diseases as Duchenne muscular dystrophy.