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."
