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Viral Vector Delivers Dystophin Gene To Mouse Muscle

University of Michigan
412 Maynard St. Ann Arbor, MI 48109-1399
October 28, 1998 (25)

DENVER---University of Michigan scientists have developed a new generation of "gutted" viral vectors that deliver the gene for dystrophin to the muscles of adult mice with muscular dystrophy without triggering their immune systems to attack the foreign virus. The vector is called a "gutted" virus, because it has been stripped of most of its original genes to make room for the large dystrophin gene.

At last year's American Society for Human Genetics meeting, Jeffrey S. Chamberlain, Ph.D., associate professor of human genetics in the U-M Medical School, reported the vector's ability to induce long-term expression of the full-sized dystrophin protein in an immuno-deficient strain of adult mice with Duchenne muscular dystrophy. At this year's meeting, Giovanni Salvatori, Ph.D., post-doctoral research fellow in Chamberlain's lab, reported the same results in mice with a normal immune system.

"Using this new version of our viral vector, we have induced stable production of dystrophin for at least four months in muscle fibers of adult, dystrophic mice with normal immune systems," Salvatori said. "Removing a reporter gene called LacZ from the vector was the key to reducing the vector's strong immunogenic effect. Although we still see a small immune response, it peaks after 30 days and does not appear to adversely affect the ability of mouse muscle to take up the vector and produce dystrophin."

A new cell packaging line, also under development at the U-M, will make it possible to produce large amounts of the vector without contamination by other proteins or viruses that could trigger an immune response in humans, according to Salvatori.

The result is significant, because stability and immune response were two major problems that remained to be solved in mice before the U-M's dystrophin vector could be tested for safety and effectiveness in humans. Chamber
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Contact: Sally Pobojewski
pobo@umich.edu
734-647-1844
University of Michigan
30-Oct-1998


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