As an experimental treatment for AIDS, cancer, and inherited genetic diseases, gene therapy--replacing defective genes with working copies or adding genes that make cells better at fighting disease--is growing ever more fashionable. With hundreds of millions of dollars invested in research and 106 clinical trials approved, gene therapy would appear at first glance to be one of medicine’s most promising fields.
Indeed, 1995 produced encouraging results from three highly publicized trials involving children with a form of severe combined immunodeficiency, or SCID. The children lacked an enzyme, ADA, that protects T cells from a toxin in the body. In the three trials--at the National Institutes of Health, Childrens Hospital in Los Angeles, and the H. S. Raffaele Scientific Institute in Milan, Italy--a virus carried a healthy gene for the enzyme into blood cells taken from the children, and the blood cells were then returned to the body. The researchers in charge of the trials reported this past year that in all the children, many of the T cells carried the healthy gene and that all the children were in good health. But that good health could not be conclusively linked to the gene therapy; for ethical reasons, the children were still given the old treatment for ADA deficiency, consisting of regular injections of a synthetic form of the enzyme. In other trials, too, there has been no unambiguous evidence that gene therapy has worked.
Part of the problem may be the gene-delivery method. Ninety-two of the 106 clinical trials have used crippled viruses to carry genes into cells, and though this method seems to have worked in the SCID trials, in other cases the viruses have caused trouble. Some have provoked inflammation and an immune response that destroyed both the virus and the cells to which it delivered genes; some threaten to damage parts of the cells’ chromosomes.
So even as some researchers are charging ahead with clinical trials, others are trying to perfect better methods of gene therapy. Here are three ideas now under investigation.