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Scientists force viruses to evolve as better delivery vehicles for gene therapy

Viruses and humans have evolved together over millions of years in a game of one-upmanship that, often as not, left humans sick or worse.

Now, a University of California, Berkeley, researcher has shown that viruses - in this case, a benign one - can be forced to evolve in ways to benefit humans.

The adeno-associated virus, or AAV, is a common, though innocuous, resident of the body that has received a lot of attention in recent years as a possible carrier for genes in gene therapy. Because as many as 90 percent of people already have the virus, however, their immune systems are primed with antibodies to quickly tackle and neutralize it, thwarting any attempt at gene therapy.

UC Berkeley's David Schaffer, associate professor of chemical engineering and a member of the Helen Wills Neuroscience Institute, with colleagues Narendra Maheshri, James T. Koerber and Brian Kaspar, decided to speed up the process of viral evolution and direct the change in a way that would allow the virus to slip past the body's immune defenses, making it a more viable vehicle for gene therapy. In essentially two generations of accelerated evolution, requiring about two months of lab work, they succeeded.

Schaffer and his team at UC Berkeley and at Ohio State University report their success in the current issue of Nature Biotechnology.

"Directed evolution has mainly been done to change the activity of an enzyme - to make it more effective toward a new substrate or better able to catalyze a reaction, for example - or to make antibodies better binders against specific targets," said Schaffer, who also is an affiliate of the UC Berkeley wing of the California Institute for Quantitative Biomedical Research (QB3). "In the viral realm, this approach is essentially untapped."

This technique could be used to improve many other characteristics of AAV to make it a better delivery vector for genes.

"We think there are a huge variety of new problems
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Contact: Robert Sanders
rsanders@berkeley.edu
510-643-6998
University of California - Berkeley
7-Feb-2006


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