Gene transfer to skeletal muscle

Abstract

Muscle tissue is an important target for gene therapy applications due to the large number of disorders of skeletal and cardiac muscle. These include inherited disorders such as Duchenne muscular dystrophy (DMD) and acquired disorders such as heart failure and age‐associated muscle weakness (sarcopenia). A potentially powerful approach to treating these various conditions involves delivery of a gene or genes to the affected muscles. In the case of a genetic disorder, the goal may be to deliver a normal version of the defective gene. In other cases, benefit might result from delivery of a gene that could augment normal muscle function, such as a growth factor gene. Other applications include delivery of DNA fragments that could modulate gene expression or lead to correction of a genetic mutation. Since muscle tissue represents nearly 40% of the total body mass, gene transfer to muscle is an enormously challenging proposition. Consequently, numerous types of gene or DNA vectors and delivery strategies are being explored for gene therapy of muscle disorders. No single gene vector or delivery method is likely to be universally applicable for all conditions, but some have been developed to greater degrees than others. This article briefly reviews the major vectors and delivery methods currently being developed for gene therapy of muscle diseases.