Section 1. Fundamentals

Chapter 2. Genetics

Topics: Introduction | Gene Abnormalities | Gene Technology | Gene Therapy

Gene Therapy

Gene therapy involves the insertion of normal copies of genes into the cells of a person with a specific genetic disease. The normal copies can be manufactured, using PCR, from normal DNA donated by another person. Because most diseases are recessive, in most cases an inserted copy of a normal gene is dominant and takes over the functions controlled by that particular gene.

There are two forms of gene therapy--somatic and germline. In somatic therapy, gene expression is corrected in the patient but does not affect future generations (somatic refers to the entire body other than the germ cells). In germline therapy, the beneficial genetic change is inserted into the cells responsible for reproduction (eggs or sperm, which are also known as germ cells). Thus, the beneficial changes are passed on to the next generation. However, germline therapy is generally considered an inappropriate way to deal with genetic diseases because of ethical issues, cost, lack of research in humans, lack of knowledge about whether changes would be maintained in the growing embryo, and the relative ease of using somatic therapy. Currently, gene therapy is most likely to be effective in the prevention or cure of single-gene defects, such as cystic fibrosis.

The transfer of the normal DNA into abnormal cells can be done in a number of ways. One way is to use a virus. The normal DNA is spliced into the virus, which then infects the abnormal cells, thereby transmitting the DNA into the nucleus of those cells. Another method uses liposomes, which are tiny sacs containing the DNA that are absorbed by the abnormal cells and thereby deliver their DNA to the cell nucleus. A third method is called naked plasmid DNA injection, in which plasmid DNA (a special circular form of DNA) is injected into a muscle.

A totally different approach to gene therapy is the use of antisense technology, in which, rather than altering abnormal genes, the abnormal genes are simply switched off (antisense drugs combine with specific sequences on the DNA that prevent the affected genes from functioning). Antisense technology is currently being tried for cancer therapy but is still very experimental.

Gene therapy is also being studied experimentally in transplantation surgery; by altering the genes of the transplanted organs, the organ recipient would not need to receive immunosuppressive drugs, which have significant side effects.