People with HIV have to take a cocktail of drugs daily to keep the lethal virus in check. But a novel gene therapy approach, now under development at Stanford, could make patients resistant to the virus and free them from this lifelong dependence on drugs, which have adverse side-effects.
In a new study, the researchers describe their technique of using “genome editing” to make T cells, key cells of the immune system, resistant to the virus. In studies done in the lab, the technique effectively blocked the virus from entering the cells through one of two receptors, known as CCR5 and CXCR4. These are the two common entry points for the virus.
In one instance, the researchers used genetic manipulation to deactivate the CCR5 receptor gene. And for added protection, they were able to introduce three known anti-HIV genes into the receptor genes. This blocked both CCR5 and CXCR4. These modified T cells had more than 1,200-fold protection, and in some instances more than 1,700-fold protection, against HIV; unmodified cells succumbed to infection in a matter of weeks, the researchers reported.
The research is still in the early stages and has to go through animal testing, as well as clinical trials. But it is a very encouraging step forward in the field of gene therapy for HIV, Matt Porteus, MD, the lead investigator told me.
“I feel this is a significant improvement in the first generation application. So I’m very excited,” he said.
Interestingly, as I left Porteus’ lab, located in the Lorry I. Lokey Stem Cell Research Building, I ran into another HIV researcher and mentioned the work, which was entirely new to him. That’s how innovative this technique is.
Porteus, a pediatrician, is interested is using the approach to treat other diseases as well. A hematologist and cancer biologist, he treats children at Lucile Packard Children’s Hospital and is hoping some of his patients, such as those with sickle cell anemia, might someday benefit from a gene therapy approach along these lines.
