Muscle as a metabolic factory for gene therapy

Abstract

Since the identification of gene transfer vectors that can efficiently transduce skeletal muscles, the muscle has been targeted in gene therapy strategies to act as a factory of therapeutic gene expression for the treatment of metabolic diseases. The easy accessibility of the skeletal muscle for vector delivery procedures and the ability of the muscle cells to both express and secrete proteins encoded in gene therapy vectors makes the muscle an ideal platform on which to develop gene therapy strategies for the treatment of metabolic diseases of the muscle as well as those diseases that do not involve muscle pathology. We discuss herein current gene therapy strategies focused on using the muscle as a biosynthetic factory. In particular, we will discuss preclinical work for two metabolic myopathies, McArdle and Pompe diseases, and updates on muscle-targeted gene therapy clinical trials for the treatment of other inborn errors of metabolism, alpha-1-antitrypsin deficiency and hemophilia B.