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UF researchers develop improved gene therapy agent
Date:5/19/2008

GAINESVILLE, Fla. Replacing one amino acid on the surface of a virus that shepherds corrective genes into cells could be the breakthrough scientists have needed to make gene therapy a more viable option for treating genetic diseases such as hemophilia, University of Florida researchers say.

Reporting in the journal Proceedings of the National Academy of Sciences today (May 19), UF geneticists say they have developed a new version of the adeno-associated virus used in gene therapy that works about 30 times more efficiently in mice than vectors scientists currently rely on.

The discovery could be the solution to a problem that has plagued researchers and doctors using AAV as a gene therapy vector how to administer enough of the gene-toting virus to yield a therapeutic benefit without triggering an attack from the bodys immune system, says Arun Srivastava, Ph.D., the George H. Kitzman professor of genetics and the chief of cellular and molecular therapy in the UF College of Medicine department of pediatrics.

AAV is considered ideal for gene therapy because it possesses the viral ability to infect cells yet does not lead to disease. But scientists discovered they had to administer trillions of AAV particles for the corrective gene to take root in a cells nucleus and begin working.

Based on our studies and those of others, its become clear that the reason you need so much is because about half the AAV particles get stuck in the cytoplasm, said Srivastava, the senior author of the study and a member of the UF Genetics Institute. It doesnt get to the nucleus very efficiently. The reason for that is obvious. AAV is seen by the body as an invading protein and it tries to block it.

The body mistakenly tags many AAV particles as junk proteins and sends them into cellular trash cans called proteasomes, where they are destroyed, Srivastava said. And a particular amino acid, tyrosine, is to blame.

Tyrosine has as pa
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Contact: April Frawley Birdwell
afrawley@ufl.edu
352-273-5817
University of Florida
Source:Eurekalert

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