Fas (CD95, Apo-1) ligand gene transfer

Gene therapy represents a new form of medical intervention that relies on direct transfer of genetic materials into patients. Although initially envisioned as a treatment for genetic diseases, gene therapy is currently being explored for a wide range of acquired disorders including cancer, cardiovascular diseases, arthritis, and neurodegenerative disorders. Since most acquired diseases are not caused by single gene mutations, the choice of therapeutic genes is crucial for the success of the gene therapy. In this review, we discuss the progresses that have been made and problems that remain to be resolved in using Fas (CD95, Apo-1) ligand gene for the treatment of acquired disorders. Fas ligand is a member of the tumor necrosis factor family that can induce both apoptosis and activation of various cells. While Fas ligand gene transfer indeed eliminates cancer cells and inflammatory cells through apoptosis, it also kills normal cells and initiates inflammation in certain tissues. Thus, new strategies that can modify the apoptotic or proinflammatory activities of the FasL will help to fully realize the potential of the FasL gene therapy.