Retinal targeting by Anc80LIVIA CARVALHOThe immune system is designed to protect the body, but it sometimes gets in the way—by rejecting potentially life-saving blood transfusions or organ transplants, for example. Because one of the most commonly used methods for delivering gene therapies involves viruses as vectors, scientists developing such treatments are working to circumnavigate the host immune response.
Adeno-associated viruses (AAVs) have shown promise as gene-therapy delivery vehicles in clinical trials evaluating treatments for hemophilia and a genetic form of blindness. Problem is, anywhere from 30 percent to 90 percent of people have already been exposed to AAVs—which are not pathogenic—and have developed immunity to them, said Luk Vandenberghe of the Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary in Boston. As a result, they are ineligible for AAV-based therapies. “And it could, for some of these diseases, actually be a life-or-death differentiation—enrolling in a gene therapy trial or not,” he said.
In an effort to generate gene therapy vectors that could evade the immune system, Vandenberghe and his colleagues deduced the evolutionary history of today’s AAVs. They then synthesized the ...
