Current state and prospects for gene therapy of Duchenne muscular dystrophy in the world and in Russia

Failure of drug therapy of Duchenne muscular dystrophy (DMD) stimulated intense search for adequate methods of gene therapy (GT) which would ensure effective delivery of the dystrophin (D) gene, its long-term persistence in transfected cells, and its expression in muscle fibers. The main results of the experimental GT of DMD with the use of viral and nonviral delivery of the D gene into muscles of biological models are discussed. Delivery of a mini-gene of D with a specific muscle promoter using a modified adenoassociated virus is currently the most promising method, which will soon be available for clinical trials. The main results of the studies on the DMD GT in Russia are summarized. The results of experiments on genetic transfection of mdx mice with marker genes and various constructions with the D gene are outlined. The genes are delivered into muscles by means of gene gun, electroporation, viral oligopeptides, liposomes, microspheres, lactoferine, and other nonviral vehicles. It is emphasized that consolidation of funds and efforts of all Russian laboratories dealing with gene and cell therapy of DMD are necessary to complete the experiments and start clinical trials.