Gene therapy - Clinical considerations

Gene therapy can be defined as the introduction of nucleic acid into cells to ameliorate a disease process. To date there have been more than 313 tria ls with more than 2000 patients enrolled. The majority of these trials are Phase I or Phase IT. and have target diseases of either cancer or acquired immunodeficiency syndrome using retroviral and retroviral vectors. The choi ce of molecular target and the means of delivery have varied and chosen on the basis of the specific indication. Until recently the risks associated w ith treatment had been under appreciated. The first fatality associated wit h gene therapy occurred in September 1999 in which an adenoviral vector was used in the treatment of a patient with orthnithine transcarbamylase defic iency. Subsequent to this report, other reports have surfaced suggesting th at reporting of previous nonfatal reactions may have been minimized, Safety must be considered in relation to the disease process and to alternative t reatments available. It may be easier to rationalize placing patients at ri sk who are facing a fatal disease process without effective alternative the rapies. The ultimate goal of gene therapy will be the injection of a vector that has a specific target cell and that will be regulated by physiologic signals. Such a goal will require major improvements in the currently avail able delivery systems or the development of novel vectors.