Nonviral Gene Delivery

Abstract

Gene therapy became a clinical reality when Rosenberg et al. (1) treated two young patients with adenine deaminase (ADA) deficiency with a retroviral vector that had been biotechnologic ally manipulated to encode for human ADA. Since 1990, approx 300 clinical trials, with a total of over 2000 volunteers or patients participating, have been conducted. Viral vectors predominate over synthetic approaches, which account for approx 25% of the 2100 patients enrolled in clinical gene therapy protocols worldwide (2). Although originally conceived as a therapy for genetic diseases, i.e., replacement of a defect or missing gene, the concept of gene therapy has since been dramatically expanded to include the gene as a drug and the gene as a vaccine. Acute inflammatory diseases, such as adult respiratory distress syndrome could benefit from the temporary overexpression of genes that produce antioxidants, e.g., superoxide dismutase/catalase, or interact with the prostaglandin/leukotriene cascade (3). Transfection of cells, specifically, cancer cells, with genes that generate presentation of nonself immune-responsive moieties at the cell surface, has led to the development of DNA vaccines, to date perhaps the most successful and promising subfield within the area of gene therapy (4).