Can Gene Therapy Cure HIV?

Why It Matters

There is no cure for HIV, which can cause AIDS. In 2012, 1.6 million people died of AIDS-related illnesses.

The immune cells of HIV patients can be genetically engineered to resist infection, say researchers. In a small study in humans, scientists report that by creating a beneficial mutation in T cells, they may be able to nearly cure patients of HIV.

In a study published in the New England Journal of Medicine on Wednesday, researchers report that they can use genome editing to re-create the rare mutations responsible for protecting about 1 percent of the population from the virus in infected patients. They report that some of the patients receiving the genome-modifying treatment showed decreased viral loads during a temporary halt of their antiretroviral drugs. In one patient, the virus could no longer be detected in his blood.


Zinc-finger nucleases are one of a few genome-editing tools that researchers use to create specific changes to the genomes of living organisms and cells (see “Genome Surgery”). Scientists have previously used genome-editing techniques to modify DNA in human cells and nonhuman animals, including monkeys (see “Monkeys Modified with Genome Editing”). Now, the NEJM study suggests the method can also be safely used in humans.

From each participating patient, the team harvested bone marrow stem cells, which give rise to T cells in the body. They then used a zinc finger nuclease to “break” copies of the CCR5 gene that encodes for proteins on the surface of immune cells that are a critical entry point of HIV. The stem cells were then infused back into each patient’s bloodstream. The modification process isn’t perfect, so only some of the cells end up carrying the modification. “About 25 percent of the cells have at least one of the CCR5 genes interrupted,” says Edward Lanphier, CEO of Sangamo Biosciences, the Richmond, California, biotech company that manufactures zinc finger nucleases.

Because the cells are a patient’s own, there is no risk of tissue rejection. The modified stem cells then give rise to modified T cells that are more resistant to infection by HIV, say the researchers.

One week after the infusion, researchers were able to find modified T cells in the patients’ blood. Four weeks after the infusion, six of the 12 patients in the study temporarily stopped taking their antiretroviral drugs so the researchers could assess the effect of the genome-editing treatment on the amount of the virus in the patients’ bodies. In four of these patients, the amount of HIV in the blood dropped. In one patient, the virus could no longer be detected at all. The team later discovered that this best responder had naturally already had one mutated copy of the CCR5 gene.

Patients who carry one broken copy of the CCR5 progress to AIDS more slowly than those who don’t, says Bruce Levine, a cell and gene therapy researcher at the University of Pennsylvania School of Medicine and coauthor on the study. Because all of the cells in that best-responder patient already carried one disrupted copy of CCR5, the modification by the zinc finger nuclease led to T cells with no functional copies of the gene. That means the cells are fully resistant to HIV infection. The team is now working to increase the number of immune cells that end up carrying two broken copies of CCR5.

ORIGINAL: Technology Review