Is there a future for gene therapy?

The requirements for successful gene therapy are stated and brief details are given of the gene therapy trials in humans which have been approved by the NIH during the years 1989-1997. An indication is given of the gene therapy trials that have been carried out in animal models of Duchenne muscular dystrophy with emphasis on the Golden Retriever dog model. Problems facing somatic gene therapy for inherited muscle diseases are predominantly the following: the extent of the spread of expression from the injection site, the duration of expression and the need for systemic delivery. Brief details of the problems are given and possible ways of overcoming the difficulties are outlined. These include the use of multiple intramuscular injections, increasing the permeability of the extracellular matrix of muscle, inducing mitosis in myoblasts, the use of ex vivo gene transfer, using modified viruses as vectors or synthesized transporter molecules, the use of mechanisms which combat the action of killer T cells, upregulation of isoforms or of alternative proteins such as utrophin for dystrophin and the use of genetic correction methods such as the use of antisense oligonucleotides. It is concluded that there is a potential future for somatic gene therapy in the inherited muscle diseases.