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Ancient DNA helps UF researchers unearth potential hemophilia therapy

viral gene therapy has been associated with medical complications, and a few human patients have died as a result.

Instead, UF researchers used a novel nonviral approach, employing a strand of DNA present in modern-day fish called a transposon to transport the gene directly into the DNA of the mice. Nonviral therapy is thought to be safer, Fletcher said.

Transposons have the natural ability to bounce to different positions in DNA, allowing them to chauffeur genes into the cell. The transposon UF researchers used is one of a few that work in mammals, but until University of Minnesota scientists discovered it in 1997, it had remained hidden in the DNA of fish like trout for 15 million years. Years of mutations in the genetic code had buried the transposon, silencing its ability to issue molecular marching orders.

Fletcher and researchers Li Liu, M.D., Ph.D., an adjunct postdoctoral associate in the department of pharmacology and therapeutics, and Cathryn Mah, a UF assistant professor of pediatric cellular and molecular therapy, used the transposon to inject the gene into endothelial cells, which line blood vessels and other parts of the body. This was unique, Fletcher said, because the liver is generally considered the body's powerhouse for producing the protein needed to keep hemophilia at bay. The study showed that these endothelial cells also can produce enough protein to correct the problem, he said.

"I think endothelial cells are potentially a very important cell to make factor VIII," said Katherine P. Ponder, M.D., an associate professor of medicine and a hemophilia researcher at Washington University in St. Louis. "They're a very attractive cell type to express it."

It also was the first time researchers attempted such an approach on an animal so young. In adult mice, the immune system normally views clotting protein as an invader and rejects it after traditional gene therapy. But UF researchers bypassed this immune respo
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Source:University of Florida


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