Introduction to Gene Therapy

Abstract

Gene therapy as we understand it nowadays was conceived during the early and mid part of the twentieth century. At first, it was considered a revolutionary biomedical procedure, which could potentially cure any disease for which the molecular bases were understood. Since then, gene therapy has gone through many stages and has evolved from a nearly unrealistic perspective to a real life application. After several decades of research, a wide range of gene delivery vectors have been engineered and successfully tested in many animal models of human disease. However, clinical efficacy in humans could not be shown until the beginning of this century after its successful application in small-scale clinical trials to cure severe immunodeficiency in children. In these particular clinical trials, a retrovirus vector based on mouse leukemia virus was used, and their successes were overshadowed some time later by the occurrence of vector-related leukemia in a number of treated children. These fatal secondary effects clearly showed that the safe application of gene therapy critically depends on our understanding of vector engineering. In this context, lentiviral vectors have appeared, with improved efficiency and, apparently, increased biosafety. Very recently, the first clinical trials with lentivectors have been carried out with some success. In this chapter, we briefly define gene therapy, and describe the main scientific steps, which culminated in the engineering viral vectors in gene therapy, and place them in the context of current human therapy.