Current Status and Future Prospects of Gene Therapy

Abstract

Since the discovery of DNA and the subsequent recognition that genetic defects (either inherited or acquired) can be responsible for various disease states, the concept of gene therapy has been extremely appealing. However, despite intensive work in this field of medicine, gene therapy has yet to make a major impact on the treatment of patients. Many technical challenges exist that must be overcome before gene therapy can be put into widespread practice. The gene delivery system (vector) encounters extracellular and intracellular barriers, must be nontoxic and nonimmunogenic, and must allow sufficient expression of the gene of interest. Many vectors have been created in attempts to overcome these problems; however, the ideal expression vector for use in humans has yet to be identified. Both inherited and acquired diseases may potentially benefit from gene therapy. X-linked severe combined immunodeficiency-X1 is an inherited disease in which gene therapy is not only being actively pursued as a potentially curative treatment, but some exciting progress has been made in recent years. In addition, acquired diseases, such as cancer, often have defined genetic alterations and, thus, are potential candidates for treatment with gene therapy. For example, malignant melanoma, a tumor that is notoriously chemoresistant, may avoid immune recognition by progressive loss of cell surface MHC class I molecules. Allovectin-7® is a DNA plasmid containing the gene encoding human MHC class I HLA-B7. Early phase I/II studies of Allovectin-7® in patients with metastatic melanoma have shown some encouraging results. It is one of many examples of how gene therapy may affect cancer treatment in the near future.