Emerging research has made an exciting step toward the prevention and cure of HIV/AIDS. At least 36 million people have died from HIV/AIDS since its first report in 1981. One in six HIV-positive individuals is unaware of his or her status. The virus infects and disables immune cells — the T helper cells which orchestrate immune responses — and makes the individual highly susceptible to a range of other infections. A regimen of antiretroviral drugs is used to fight the infection, but this therapy is extremely expensive, sometimes ineffective, and can cause severe side effects.
Recent research at the University of Pennsylvania tested a therapy based on a rare genetic mutation which disables the CCR5 receptor which HIV uses to infect T helper cells. A lucky one percent of people are immune to HIV/AIDS because they have two copies this mutated gene, the CCR5-knockout allele. This means that these people have none of the receptors that HIV uses to enter the cell. It was one of these genetically lucky individuals from whom the famous “Berlin patient” received a bone marrow transplant that cured him of the virus. In order to confer HIV immunity without expensive and invasive bone-marrow transplant surgery, researchers have begun modeling the CCR5 mutation in the laboratory.
Sangamo Biosciences, Inc. developed a method for synthetically disabling the CCR5 gene; the results of the Penn critical trial, which were published on March 6th, document its success. Researchers used zinc finger nucleases — DNA scissors — to genetically manipulate T cells from 12 HIV-positive individuals. Zinc finger nucleases disable specific genes such as those which make the CCR5 receptor. After injection with the modified (and CCR5-less) T cells, half of the participants stopped antiretroviral therapy. Those treated with the mutated T cells had a higher concentration of functional T cells, suggesting that limited immunity was conferred by disabling the CCR5 receptor. However, critics question whether these DNA scissors are specific enough: they worry that other DNA may be damaged by accident.
Although most patients slowly were reinfected by the virus and their T helper cell concentrations lowered, one patient was virus-free for the entire 12 weeks the study observed. Many look forward to further research into this genetic manipulation: it may lead to a cure to HIV.