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Scientists Evolve Virus to Slip Past Human Immune System

In a project that could benefit human health, scientists forced the evolution of a common virus so that it can avoid the human immune system, making it potentially useful as a delivery vehicle for gene therapy.

The adeno-associated virus, or AAV, infects about 90 percent of humans. Our immune system is adept at dealing with it. And because antibodies attack and neutralize the virus so readily, it's rendered useless for delivering drugs.

So researchers sped up the virus' evolution, forcing two generations within about two months.

Untapped approach

Similar so-called "directed evolution" has been done before to change activity of specific enzymes or to make antibodies bind better with target on cells, but in the viral realm, "this approach is essentially untapped," said project leader David Schaffer at the University of California, Berkeley.

Already Schaffer and his colleagues are pondering other beneficial uses for the new type of directed evolution.

"We think there are a huge variety of new problems we could address as well, such as targeting the virus to cells it is ordinarily not good at getting into, or speeding its transport through the body," Schaffer said.

There's a potential downside, too. Schaffer acknowledged that the technique could be used to help deadly viruses evade the immune system. But other and easier techniques already allow this frightening possibility, he said.

The project details

The researchers created mutant viruses by altering their DNA using proven techniques. Then they exposed the mutants to blood serum from rabbits immunized against AAV—the serum contained many types of antibodies to AAV. Only the mutant viruses that were able to evade the antibodies survived. The process was repeated with the survivors.

The emerging mutants survived after being injected into mice that had a thousand times the level of antibodies needed to destroy the wild AAV.

The technique was effective because it did not try to predict how the experiment should be done, but rather simply let nature play the key role while scientists forced the evolutionary setting, Schaffer said.

Now there's more work to be done:

"This virus is kind of a gift from nature, a very safe and efficient virus, but nature never evolved it to be a human therapeutic," he said. "So, in a sense, we have to re-evolve it for that purpose."

Robert Roy Britt
Rob was a writer and editor at Space.com starting in 1999. He served as managing editor of Live Science at its launch in 2004. He is now Chief Content Officer overseeing media properties for the sites’ parent company, Purch. Prior to joining the company, Rob was an editor at The Star-Ledger in New Jersey, and in 1998 he was founder and editor of the science news website ExploreZone. He has a journalism degree from Humboldt State University in California.