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$1.6 million grant
HIV/AIDS gene therapy work continues with NIH funds
Thursday, Feb. 21, 2013
By Lorraine A. Nelson, College of Pharmacy
PULLMAN, Wash. – Grant D. Trobridge of Washington State University has received a $1.6 million grant from the National Institutes of Health to continue investigating the use of gene therapy for HIV and AIDS, an area where he has had success.
In the therapy, genes that interfere with the virus’s ability to replicate are delivered to a patient’s blood stem cells. A significant roadblock has been inefficient transfer of new DNA to the patient, but Trobridge and his colleagues have spent years developing a more efficient transfer agent to deliver anti-HIV genes to blood stem cells in a mouse model.
There is evidence that stem cell therapy for HIV/AIDS can be effective. A blood stem cell transplant done in Germany is believed to have erased the patient’s HIV. He has been free of the disease for five years and that has sparked hope that gene therapy could be a cure for AIDS (acquired immune deficiency syndrome).
The transplant was a bone marrow transplant and involved a donor with a rare genetic condition. It provides natural resistance to HIV; that resistance transferred to the patient and his HIV disappeared. (See an article at http://nyti.ms/uLZqyn)
"The success in this patient is remarkable,” Trobridge said. However, it is infrequent that there will be such a donor who is also a match for the transplant, he said.
The incidence of new cases of HIV – or human immunodeficiency virus, a disease of the immune system – has slowed since an effective drug therapy became available in 1996, according to the U.S. Centers for Disease Control and Prevention.
"Drug therapy has greatly reduced the progression of HIV to AIDS, but the side effects can be severe and the emergence of drug resistance is a problem,” Trobridge said. "Patients who have stopped taking the drugs experience a rapid resurgence of the virus.”
The goal of his research with the new five-year grant is to continue to improve the safety and efficacy of his approach.
"Different investigators have developed different genes that inhibit HIV,” Trobridge said. "We are trying new combinations of those genes to see how that works.”
Ironically their transfer agent – known as a vector – is a virus related to HIV. Viruses are often used to introduce new genetic material, and Trobridge is using a type known as a "foamy virus.”
It may seem odd that scientists would use transfer agents such as foamy viruses, but they work well because they have evolved over millions of years to efficiently deliver genes, Trobridge said. Unlike HIV, foamy viruses are not known to cause any disease.
One goal of this research is to compare the safety of foamy virus vectors to the HIV vector and other vectors in the HIV class, known as lentiviral vectors.
Trobridge also will use bioinformatics – lots of human gene data accessible via computer – to study where the virus integrates and also to compare different vector designs to see if one is safer than another.
Trobridge is an assistant professor of pharmaceutical sciences in the College of Pharmacy. Before coming to WSU in May 2010, he was a staff scientist at the Fred Hutchinson Cancer Research Center in Seattle and a research assistant professor in the Department of Medicine at the University of Washington. He has a Ph.D. in microbiology from Oregon State University.