Genetically Modified Cells Could Prevent Death From HIV/AIDS, Study Finds
Using genetic modification to treat HIV could create cells that are resistant to the two major types of the virus, preventing it from evolving into AIDS, according to a new study.
Researchers at the Stanford University School of Medicine and the University of Texas at Austin used a method known as targeted trait stacking to paste a series of HIV-resistant genes into T cells - immune cells targeted by the AIDS virus - blocking infection as HIV tries to enter the cell by altering the two major entry ways into the cells, CCR5 and CXCR4. Any truly useful treatment for HIV would have to protect against entry via both of these receptors.
"We inactivated the CCR5 gene, and then introduced 3 additional genes," Dr. Matthew Porteus, an associate professor of pediatrics at Stanford and lead investigator in the study, told ABC News. "When cells had all four of these traits, we found that after 25 days the cells were completely resistant to both types of HIV."
One of the major obstacles to treating HIV is the high mutation rate of the virus. Patients must use a cocktail mix of drugs, known as Highly Active AntiRetroviral Therapy (HAART), in order to fight the virus at different stages.
"HIV is a great shape shifter," said Sara Sawyer, an assistant professor of molecular genetics and microbiology at the University of Texas at Austin and co-author of the study. "It can come up with new solutions, so a single drug does not work very well. That's why HIV patients are given multiple drugs at once."
The T cells have been engineered to contain a cocktail of genes, analogous to the cocktail of drugs that HIV patients are given. They informally call it genetic-HAART, and it would bolster a patient's immune system with HIV-resistant T cells. While other non-resistant cells were being killed by the virus, these supplemented T cells would remain, strengthening the patient's immune system and serving as an alternative to traditional HIV treatments.
"This method would give people a protected reservoir of T cells that would thwart off immune system collapse, and the secondary infections that give rise to AIDS," said Sawyer.
The next steps in refining this particular approach to combating HIV/AIDS include finding the right cocktail of genes, and inserting them into T cells from AIDS patients. These modified T cells could then be used in animals to determine whether or not they remain resistant over time. These steps are required by the Food and Drug Administration before it can approve clinical trials, which could take 3-5 years.
"To develop novel therapies you have to be an optimist," said Porteus. "The findings in this study are a proof of concept; we've proven this could work."
The study was funded by the Foundation for AIDS Research and will be published in the Jan. 29 issue of the journal Molecular Therapy.