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With an eye on safety, UF experts explore cellular mechanisms of gene therapy

GAINESVILLE, Fla. - In an era of heightened concern about gene therapy safety, a new University of Florida study provides reassurance that corrective DNA can be administered without simultaneously causing harmful genetic changes.

The findings, published in the March 27th issue of the Proceedings of the National Academy of Sciences, begin to answer an important question: Does an inserted package of genetic material actually incorporate itself into the receiving cell's DNA?

Scientists had worried that if the genetic material did integrate into the cell's own genetic wiring by becoming part of a chromosome, it potentially could disrupt the function of a healthy gene or lead to tumor development. The new research shows that in mice, new genes delivered inside a modified adeno-associated virus dwell independently in cells, reducing the risk of such problems.

"Even though we have never seen any problems from the AAV vector we use for gene therapy, we needed to know where the delivered DNA is going within the cell," said Sihong Song, lead author of the paper and a research assistant professor in the UF College of Medicine's pediatrics department. "We need to understand how it really works, so that we can design safer and more effective gene therapy vehicles."

Composed of DNA, genes are the basic unit of inheritance and provide the instruction manual for how to make the body function. If a person has inherited a faulty version of a critical gene, lifelong disease may result. In gene therapy, researchers seek to reduce or eliminate disease symptoms by providing a patient with working copies of a corrective gene so that cells in the affected tissues may begin following a new set of marching orders.

At UF and elsewhere, a growing number of laboratory experiments and clinical trials are employing AAV to essentially "infect" cells with corrective DNA. A common virus that has not been linked to any illness, AAV can be modified so that it includes a wi
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Contact: Victoria White
vjwhite@tampabay.rr.com
352/344-2738
University of Florida
5-Apr-2001


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