Somatic gene therapy. Present situation and future perspective.

Abstract

The ultimate goal in the management of inherited as well as acquired diseases is a rational therapy with the aim to eliminate the underlying biochemical defects, rather than a symptomatic treatment. Among other approaches somatic gene therapy is a promising candidate to meet these objectives and appears to have the potential to revolutionize modern medicine. Gene therapy is characterized by the transfer of genetic information to a patient through the use of recombinant DNA technology. Several strategies for the treatment of monogenetic disorders as well as chronical diseases like cancer and AIDS have been used in various somatic gene therapy projects. So far, 329 clinical studies (phases I, I/II and II) with over 2500 patients have been initiated worldwide since 1989. No significant toxicity and adverse side effects have been observed. To allow efficient transfer of the therapeutic genes, a variety of gene delivery techniques have been developed based on viral and non-viral vector systems. For the success of this technology it is vital to achieve regulated and sustained expression of foreign genes in specific target tissues. This will be crucial for the widespread application of somatic gene therapy. So far none for the gene delivery systems is able to meet the requirements of safety, efficiency and specificity demonstrating that vector research will be an important focus in the development of optimized transfer methods. From a regulatory point of view pharmaceutical DNA-products can be regarded as drugs and are therefore subject to the same regulations. Human gene therapy must, however, be limited to manipulations affecting somatic, differentiated cells to prevent the transferred gene from being transmitted to the individual's descendants. Applications for the purpose of 'enhancement' and not for the treatment of diseases are also not acceptable. Under these prerequisites, somatic gene therapy does not raise any new ethical concerns and can be interpreted as a special form of an organ transplantation. A comparison of the different regulatory situations of gene therapy in Europe and the United States demonstrates that for the European countries a uniform regulation is desired. Today somatic gene therapy is still in its infancy. It will continue to be scientifically and technically challenging until simple and effective procedures will have been developed. Demonstration of its clinical efficacy especially in the long term will have to be the next step. Looking at the history of biotechnology and the success of the biotechnology industry that is now providing safe and efficient products from recombinant DNA-technology there is little doubt that gene therapy will become a successful treatment for various indications in the next decade. The purpose of this article is to review the current status of the development in somatic gene therapy.