By transplanting blood stem cells that had been gene-edited to resist HIV infection, scientists at Fred Hutchinson Cancer Research Center were able to shrink the size of dormant viral “reservoirs” in infected animals, according to research results published last week in PLOS Pathogens. Reducing or eliminating these persistent reservoirs is a key step toward curing HIV or, to use a term borrowed from cancer, driving the virus into remission so that daily antiretroviral drugs aren’t needed.

“The number of latently infected cells, which we call the viral reservoir, was reduced,” said lead author Dr. Chris Peterson, a staff scientist in the laboratory of stem cell transplant and gene therapy specialist Dr. Hans-Peter Kiem, the paper’s senior author. “We took samples from different tissues and measured viral RNA and DNA. Both were significantly lower in transplanted animals relative to controls.”

The edited cells made up about 4% of total white blood cells—not yet enough to induce remission, Peterson said. The next step will be to tweak editing techniques so that more of the gene-altered cells “take,” or engraft, and multiply after transplantation, driving up the percentage and further driving down the reservoir.

Shrinking the reservoir is key because HIV integrates itself into the DNA of some of the longest-lived cells in the body, where it goes into a dormant state but can wake up at any time and produce new virus. Scientists at first thought that antiretroviral drug cocktails, which in 1996 transformed HIV from a death sentence to a chronic disease, would cure HIV if taken long enough. But it turns out that the drugs alone cannot clear the reservoirs. Stopping daily medication allows HIV to roar back in as little as 2 weeks.

A handful of other research teams have published results showing some reservoir reductions in animal studies: Dr. Louis Picker and colleagues at Oregon Health & Science University’s Vaccine and Gene Therapy Institute, using a vaccine; Dr. Dan Barouch and his team at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center-Harvard Medical School, using a drug that “kicks” the sleeping cells awake combined with a powerful antibody; and Dr. Mirko Paiardini and colleagues at Emory University, who reduced harmful inflammation as a means to enable the immune system to better fight the virus.

Peterson used a gene-editing technique called zinc-finger nucleases, or ZFNs, to disrupt a receptor used as a doorway by most forms of HIV (or, in this and other animal studies, a hybrid of HIV and its simian version, called SHIV). The modified stem cells were then returned to repopulate the immune system in what is known as an autologous transplant, which means using the patient’s own stem cells rather than a donor’s.

Previously, he had shown that gene-edited cells delivered via autologous transplantation were safe and would engraft and multiply in healthy, uninfected animals, a finding for which he was awarded the Young Investigator Award Special HIV Cure Prize in 2015 from the International AIDS Society and the French National Agency for AIDS Research.