Gene therapy has experienced a renaissance of late, and it’s a technology that many researchers in HIV are embracing. That’s because the ability to manipulate genes—particularly CCR5, which is known to play a role in HIV resistance—could help combat a problem that has plagued the field for years: Even when patients respond well to antiretroviral treatments, they can harbor HIV “reservoirs,” which are dormant stores of virus that can resurge at any time.
Now scientists at Fred Hutchinson Cancer Research Center in Seattle have produced compelling results from an animal trial suggesting that gene-edited stem cells from the bone marrow of patients could be a solution to the problem of HIV reservoirs. In a study of macaques infected with the related virus simian/human immunodeficiency virus (SHIV), gene editing of stem cells taken from bone marrow appeared to shrink viral reservoirs, according to a press release.
CCR5 first came to the attention of HIV researchers in 2007 after an HIV-positive patient named Timothy Brown was cured by a bone marrow transplant. Scientists later figured out that his donor had a CCR5 mutation that made his cells resistant to HIV infection.
The Fred Hutch team previously showed that it was possible to remove stem cells from the bone marrow of macaques and edit their genes to have that HIV-resistance mutation. When they transplanted the cells back into the animals, the cells multiplied.
In the new study, the team analyzed tissue samples taken from the animals and discovered the edited cells had invaded HIV reservoirs. In two of the animals, the reservoirs were undetectable, according to the paper.
The results came just two months after scientists at Case Western Reserve University and Sangamo Therapeutics announced plans for a human trial of gene-edited T cells in HIV. They’re using a technique called zinc finger nuclease gene editing to knock out CCR5 cells taken from the blood of patients. The trial is expected to enroll 20 patients.
HIV researchers have made progress in recent years unlocking the mystery of HIV reservoirs. Last year, scientists at the University of North Carolina discovered that the reservoirs can persist in white blood cells known as macrophages, which are distinct from T cells and can reside in many areas of the body, including the bone marrow.
The Fred Hutch team discovered that, over time, only 4% of the macaques’ white blood cells contained the CCR5 edit—not enough to sustain a remission of SHIV without the use of antiretroviral drugs, they said. They’re now working to improve the efficiency of their editing technique in the hopes of boosting that percentage.