Spotlight on Research 2011

May 2011 (historical)

Scientists Correct Genetic Defect in Blistering Skin Disease in Mouse Model

A new study supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) shows it may be possible to grow healthy new skin for people with a rare disfiguring skin disease called recessive dystrophic epidermolysis bullosa (RDEB). Caused by a defect in the gene coding for a protein called type VII collagen, RDEB is characterized by painful blistering of the skin and mucous membranes that leaves people prone to infections, scarring and skin cancer. Currently, the only treatment for the disease is targeted at relieving pain and improving quality of life.

While some scientists have tried using grafts of the patients’ own skin to replace damaged areas of skin in people with RDEB, these grafts have failed because they contain the same genetic defect that causes the disease. The new study, however, used skin grown from cells of patients with RDEB that were modified to express a normal type VII collagen gene.

After taking a small biopsy of skin cells called keratinocytes from people with RDEB, the scientists used a viral vector – a harmless virus engineered to deliver normal genes into cells – to correct the type VII collagen defect in the cells. The modified keratinocytes were then grown into sheets in the lab and transplanted onto laboratory mice.

Twelve months later, when the study was terminated, the skin on the mice was still attached and healthy, and the cells of the transplanted tissue continued to express the normal type VII collagen gene, says Alfred T. Lane, M.D., professor of dermatology and pediatrics at Stanford University School of Medicine, who led the study.

Now that the researchers know they can successfully transplant the modified skin on mice, the next step is to try growing larger sheets of skin and graft them back onto the people affected by RDEB, Dr. Lane says. Such skin-growing technology is already in place, and studies in adults could begin within a few months.

The greatest uncertainty with the procedure is whether the modified grafts will transplant successfully on skin that has been affected with lesions for 20 years or more, as is often the case in adults with the disease, says Dr. Lane. His goal, eventually, is to test the modified grafts on children in hopes of treating the disease before it has caused extensive or long-term damage.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at


Siprashvili Z, Nguyen NT, Bezchinsky MY, Marinkovich MP, Lane AT, Khavari PA. Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Hum Gene Ther. 2010 Oct;21(10):1299-310.