MYOBLAST-BASED GENE THERAPIES

Recent identification of the genetic causes of several neuromuscular d isorders has aroused interest in gene therapy in skeletal muscle. The genetic constitution of skeletal muscle can be altered by a number of means. Myoblasts can be used to introduce new genes, endogenous or exo genous, into muscle fibres during growth and repair. DNA expression-pl asmids can be directly transfected into a small proportion of muscle f ibres, showing persistent expression despite their lack of genomic int egration. Recombinant replication deficient adenoviruses are efficient vectors into myoblasts and developing muscle fibres; again, the intro duced constructs show long-term episomal persistence and expression. B y contrast, recombinant replication deficient retroviruses efficiently introduce constructs into the genomes of dividing myoblasts which sub sequently fuse into muscle fibres, None of the available methods provi des a practical solution for therapy of genetic muscle diseases but mi ght be useful for inducing synthesis of therapeutic non-muscle protein s by skeletal muscle