A collaborative study led by scientists from the University of California, Berkeley, and the University of Iowa has led to the conversion of a relatively benign virus into a highly infectious form, which is ideal as a carrier for gene therapy.
The researchers have revealed that the first gene therapy has been found to completely cure human cystic fibrosis lung tissue in culture.
Writing about their achievement in the online early edition of the journal Proceedings of the National Academy of Sciences, the researchers said that their success with the benign adeno-associated virus (AAV) overcomes a major problem of earlier virus-based gene therapy for cystic fibrosis, and sets the stage for tests in advanced animal models of the disease.
"I think it is worthwhile thinking about clinical therapy at the levels of infection we are achieving," said co-author David Schaffer, professor of chemical engineering at UC Berkeley.
Schaffer's pulmonologist colleague Joseph Zabner, who developed a new pig model of cystic fibrosis last year at the University of Iowa Hospitals and Clinics in Iowa City, has revealed that this model will provide a key test of the virus as a carrier of a gene to replace the mutated gene responsible for the disease.
"If we are able to show that efficient gene transfer can result in gene therapy, if we can cure the lung disease of pigs that have been genetically engineered to have cystic fibrosis lung disease, we should have a real chance of curing cystic fibrosis in humans," Zabner said in an e-mail.
Schaffer and his colleagues are also joining forces with researchers elsewhere to adapt the virus to gene therapy for other diseases, including Alzheimer's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease).
"Both of those are situations where improvements in the properties of the vehicle can have a significant impact on the success of the therapy," Schaffer said.
Cystic fibrosis (CF) is a common hereditary disease that affects the body's mucus membranes, in particular the lungs, resulting in difficulty breathing and typically in death before the age of 40 from lung or organ failure. One in 4,000 children in the United States is born with CF.
Schaffer and his UC Berkeley colleagues collaborated with Zabner's laboratory to test a technique developed by Schaffer to force the evolution of a virus in ways that make it more effective in gene therapy.