Editing immune response could make gene therapy more effective

Gene therapy generally relies on viruses, such as adeno-associated virus (AAV), to deliver genes into a cell. But the body's immune response to AAV can thwart the whole endeavor.

To overcome that obstacle, researchers at the University of Pittsburgh School of Medicine created a system that uses CRISPR in a less common way. Their system briefly suppresses genes that are related to AAV antibody production so the virus can deliver its cargo unimpeded.

"Many clinical trials fail because of the immune response against AAV gene therapy," said study co-senior author Samira Kiani, M.D., associate professor of pathology at Pitt and member of the Pittsburgh Liver Research Center (PLRC) and McGowan Institute for Regenerative Medicine (MIRM). "And then you can't readminister the shot because people have developed immunity."

"We're hitting two birds with one stone," said Mo Ebrahimkhani. "You can use CRISPR to do your gene therapy, and you also can use CRISPR to control the immune response."

When the researchers treated mice with their CRISPR-controlled immune suppression system and then exposed them to AAV again, the animals didn't make more antibodies against the virus. These animals were more receptive to subsequent AAV-delivered gene therapy compared to controls.