The pioneering report of James Watson and Francis Crick describing the helical structure of DNA spurned an upsurge of biomedical research focusing on the composition of DNA, RNA and proteins and their role in health and disease that continues today. This “molecular revolution” has markedly influenced understanding of the pathophysiology of a diverse collection of disease states ranging from cystic fibrosis (CF), inborn errors of metabolism and immunodeficiencies to cancer, cardiovascular disease and diabetes. Rapid development of recombinant DNA technology prompted sequencing of the human genome and identifying genotype-phenotype rela-tionships in human disease. Although these efforts have produced highly sophisticated, extremely sensitive diagnostic tests, the development of successful molecular therapies based upon this expanded knowledge of disease pathogenesis is still in progress.
Gene therapy is the use of nucleic acids as therapeutic medicinal compounds. The most straight-forward gene therapy strategy is to compensate for abnormal gene expression. Gene medicines can also be engineered to reconstitute a diseased organ, either by directing regeneration of specific tissues through expression of embryonic genes to induce cell growth and development or, in the case of cell-based therapies, by using natural or genetically corrected stem cells to produce healthy tissues. The field of gene therapy is still in its infancy with the first testing of this concept in the clinic occurring in 1990. This landmark trial, for adenosine deaminase (ADA) deficiency, involved the use of peripheral blood lymphocytes treated with a retrovirus expressing ADA in ADA-deficient patients (Anonymous, 1990). Ten years after treatment, lym-phocytes from one patient continued to express the recombinant transgene, indicating that the effects of gene transfer can be long lasting (Muul, 2003). Another patient developed an immune response to the gene transfer system and, as a result, did not express the therapeutic gene, illustrating the promises andproblems that afflict this innovative area of medicine. This chapter will discuss the current state of gene therapy and common approaches to gene transfer. Diseases currently subject to gene transfer applications will also be reviewed. The biology and utility of several gene transfer systems will be discussed, highlighting areas in which the pharmacist and pharmaceutical scientist can play a significant role in their development as viable medicinal products.