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Stanford researchers devise novel gene therapy technique

STANFORD, Calif. - Researchers at Stanford University Medical Center have devised a way to sneak DNA into skin cells taken from people with a potentially deadly genetic skin disorder. These modified cells later formed normal, healthy skin when transplanted onto the skin of mice. The technique, published in the advance online publication of the October issue of the journal Nature Medicine, marks the first time researchers have stably replaced the mutated gene in this disease and introduces a new gene therapy technique that could be useful in a wide range of diseases.

"We're very hopeful," said study leader Paul Khavari, PhD, associate professor of dermatology at Stanford. "This study was performed in mice but it targets grafted human disease tissue."

The technique has advantages that could one day help it treat a variety of diseases. Not only can it accommodate large genes such as those responsible for Duchene's muscular dystrophy and cystic fibrosis, but it causes the gene to integrate into human chromosomes in locations where it will continue to make protein as long as the cell is alive. In other techniques, the inserted DNA does not become part of the chromosome and eventually breaks down or else integrates in positions where the gene gets turned off.

Michele Calos, PhD, associate professor of genetics who developed the technique, said that although this paper is the first published report of her approach being used to treat one disease, early trials in other disease models look promising. "It worked great in this application and we hope it works just as well for other diseases," she said.

In the Nature Medicine paper, Khavari and Calos tested the new technique in a disease called recessive dystrophic epidermolysis bullosa (RDEB) in which the outer layer of skin is not firmly attached to the underlying layers. When children with RDEB encounter friction or trauma, the outer layer of skin simply peels away
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Contact: Michelle Brandt
mbrandt@stanford.edu
650-723-0272
Stanford University Medical Center
15-Sep-2002


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