In July, an HIV-positive man became the first volunteer in a clinical trial aimed at using Crispr gene editing to cut the AIDS-causing virus out of his cells. For an hour, he was hooked to an IV bag that pumped the experimental treatment directly into his bloodstream. The one-time infusion is designed to carry the gene-editing tools to the man’s infected cells to wipe out the virus.
Later this month, the volunteer will stop taking the antiretroviral drugs he has been using to keep the virus at undetectable levels. Then researchers will wait 12 weeks to see if the virus returns. If not, they consider the experiment a success. “What we’re trying to do is return the cell to an almost normal state,” says Daniel Dornbusch, CEO of Excision BioTherapeutics, the San Francisco-based biotech company running the trial.
The HIV virus attacks immune cells in the body called CD4 cells and hijacks their machinery to make copies of itself. But some HIV-infected cells can go dormant—sometimes for years—and not actively produce new virus copies. These so-called reservoirs are a major barrier to curing HIV.
“HIV is a difficult enemy to fight because it can insert itself into our own DNA, and it is also capable of being silenced and reactivated at different points in a person’s life,” says Jonathan Li , a doctor at Brigham and Women’s Hospital and HIV researcher at Harvard University who is not involved in the Crispr trial. Figuring out how to target these reservoirs—and doing it without damaging vital CD4 cells—has proven challenging, Li says.
While antiretroviral drugs can stop viral replication and remove the virus from the blood, they cannot reach these reservoirs, so people must take drugs every day for the rest of their lives. But Excision BioTherapeutics hopes Crispr will eradicate HIV for good.
Crispr is being used in several other studies to treat a handful of conditions that arise from genetic mutations. In those cases, scientists use Crispr to edit people’s own cells. But for the HIV trial, Excision researchers are turning the gene-editing tool against the virus. The Crispr infusion contains gene-editing molecules that target two regions in the HIV genome important for viral replication. The virus can only reproduce if it is fully intact, so Crispr disrupts that process by cutting out chunks of the genome.
In 2019, researchers from Temple University and the University of Nebraska found that using Crispr to delete those regions eliminated HIV from the genomes of rats and mice. A year later, the Temple group also showed that the approach safely removed viral DNA from macaques with SIV, the monkey version of HIV.