Clinical gene therapy for nonmalignant disease.

Gene therapy is envisioned as a potentially definitive treatment for a variety of diseases that have a genetic etiology. We reviewed trials of clinical gene therapy for nonmalignant, single-gene, and multifactorial disorders and infectious diseases, and found limited evidence suggesting that gene therapy may benefit patients who have severe, combined, immunodeficiency disorder; cystic fibrosis; coronary artery disease or peripheral arterial disease; or hemophilia. Effective gene therapy requires the targeted transfer of exogenous genetic material into human cells and the subsequent regulated expression of the corresponding gene product. Because no phase 3 randomized controlled trials have been completed that fulfill these criteria, it is difficult to correlate signs of clinical benefit with the administration of gene therapy in any disease. Additional clinical and basic research is needed to determine the future role of gene therapy.