Gene Therapy Prevents Skin Cancer

Researchers have used gene therapy to eliminate the tendency to develop skin cancer after exposure to ultraviolet (UV) light in a mouse model for the rare inherited disease called xeroderma pigmentosum (XP).

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA; www.utsouthwestern.edu) created a line of mice that mimicked the human form of XP by having a mutated form of the gene XPA in their skin cells. These cells were unable to repair damage to DNA caused by exposure to UV light. The damaged DNA caused abnormal cell growth and development leading to tumor formation and early death of the animals.

In the present study, which was published in the December 14, 2004, online edition of the Proceedings of the [U.S.] National Academy of Sciences, the investigators used a genetically engineered adenovirus vector to inject the normal human XPA gene into the skin cells of the XP mice. The animals were then exposed to UV light for a few hours over a period of several days. The treated mice did not develop skin lesions or tumors and were as healthy as normal controls five months after UV exposure.

"Gene therapy for XP has the potential to completely prevent cancer in a group of patients who otherwise may suffer no other ill effects from their genetic defect,” said senior author Dr. Errol Friedberg, professor of pathology at the University of Texas Southwestern Medical Center. "XP is a disease that lends itself well to gene therapy, for a variety of reasons. Most importantly, skin cells are highly accessible for introducing foreign genes. Also, infection of the skin with a virus carrying the gene of interest, as we did with the mice, allows for many, many cells to receive the appropriate gene. Once some of the existing technical limitations are solved, these studies can hopefully be extended to trials with human XP patients.”