Transfer of Collagen Gene May Correct Inherited Skin Disorder

This is the first step toward gene therapy to treat DEB, say the researchers. Their work was reported in the December 2002 issue of Nature Genetics.

Individuals with DEB lack type VII collagen and anchoring fibrils, structures that attach epidermis and dermis. Without these fibrils, the layers of the skin can separate, blistering and sloughing off at the slightest insult or injury. By the age of 20, people with DEB often have developed very aggressive squamous cell carcinomas.

Investigators from the University of Southern California (Los Angeles, USA; www.usc.edu) delivered and expressed full-length type VII collagen using a self-inactivating minimal lentivirus-based vector. They then used these gene-corrected cells to regenerate human skin on immune-deficient mice. Human skin regenerated by gene-corrected cells had restored expression of type VII collagen and formation of anchoring fibrils at the dermal–epidermal junction.

"This is the first demonstration of in vivo gene therapy where the genes have made a large extracellular molecular structure that you can actually see with a microscope,” explained senior author Dr. David Woodley, professor and chief of dermatology at the University of Southern California's Keck School of Medicine. "I see patients all the time who would definitely benefit from our better understanding of the basic mechanisms of skin biology,”



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