IMPLICATIONS OF MATURATION FOR VIRAL GENE DELIVERY TO SKELETAL-MUSCLE

Different viral vectors have been analyzed as gene delivery vehicles t o skeletal muscle for potentially therapeutic purposes. In this review , we evaluate the application of retroviral, adenoviral, and herpes si mplex viral vectors to deliver genes to skeletal muscle and focus on t he dramatic loss of viral transduction detected throughout muscle matu ration. Recent results suggested that there are several factors involv ed in the reduced viral transducibility of mature skeletal muscle: mus cle cells become post-mitotic in an early stage, the extracellular mat rix develops into a physical barrier, and a loss of myoblast mediation occurs since myoblasts progressively become quiescent. Approaches to improve viral gene delivery to mature skeletal muscle may include the use of particular enzymes to increase the permeability of the extracel lular matrix, the pre-treatment of the muscle with a myonecrotic agent to induce myoblast mediation, or the application of the myoblast-medi ated ex vivo gene transfer. (C) 1998 Elsevier Science B.V.