Gene Therapy for Treating Inherited Genetic Diseases

Scientists think gene therapy may be best suited for treating inherited disorders caused by single gene defects, such as cystic fibrosis, hemophilia, and sickle cell disease. In fact, some of the early successes of gene therapy have been in treating such disorders.

Gene therapy has been used to treat several children with severe combined immunodeficiency disorder (SCID), a rare and often deadly disease in which the immune system doesn't work properly. Gene therapy has restored the immune systems of more than a dozen children with this disorder. But there have also been some complications from this treatment: a few of the children have developed leukemia as a result of therapy. Such unforeseen problems have caused researchers to temper their enthusiasm and to be more cautious with further studies.

Gene Therapy and Cancer

As scientists have come to understand that cancer is the result of gene mutations, they now think that gene therapy may also be an effective way to treat cancer. Cancer is much more common than inherited genetic disorders. Because of this, interest in research into cancer gene therapy has grown in recent years. In fact, most gene therapy clinical trials are now cancer related.

Gene therapy may some day be used against cancer in many different ways. Scientists are trying to use gene therapy by:

Adding functioning genes to cells that have abnormal or missing genes. For example, cells normally have tumor suppressor genes such as p53 that help prevent cancer from developing. But many cancer cells have faulty p53 genes. We may be able to bring these cancer cells back under control by placing a working copy of the p53 gene into them.

Stopping oncogenes (or other genes important to cancer) from working. Oncogenes are mutated forms of normal genes that cause cells to divide out of control, leading to cancer. Other genes are important in allowing cancer cells to metastasize (spread to other parts of the body). Stopping these genes or the proteins they make may prevent cancer from growing or spreading.

Adding or changing genes to make cancer cells more unstable. Cancer cells often have changes in genes that would normally repair faulty DNA. This lack of DNA repair may allow them to continue to grow and divide at a rapid rate. But researchers may be able to exploit this difference between normal and cancer cells. They may be able to add or change faulty genes that normal cells can repair, but that cancer cells cannot, leading to their death.

Adding or changing cancer cell genes to make them more vulnerable to cancer treatments. Many cancer cells are resistant to chemotherapy or radiation therapy, or they become resistant over time. For example, some genes may help cancer cells to pump chemotherapy drugs out of them. Blocking these genes could make chemotherapy effective against these cells.

Making tumor cells more easily detected and destroyed by the body's immune system. The immune system is thought to play a role in keeping some cancers in check. But cancer cells have often found ways to elude the immune system, allowing them to grow out of control. Gene therapy might be helpful in 2 ways. By adding the right gene to cancer cells, doctors could 'tag' them so the immune system would then recognize and destroy them. A closely related idea is to add genes to the right immune system cells to make them better able to detect the cancer cells. This method has already yielded some promising early results.

Stopping genes that play a role in new blood vessel formation (angiogenesis) or adding genes that stop it. Tumors need a constant blood supply to grow. If this supply can be cut off, tumors may stop growing or even shrink.

Revised: 05/24/2007