In July, an HIV-positive man became the first volunteer in a clinical trial to use Crispr gene editing to extract the virus that causes AIDS from his cells. For an hour, he was hooked up to an intravenous bag that pumped the experimental treatment directly into his bloodstream. The unique infusion is designed to deliver the gene-editing tools into infected human cells to eliminate the virus.
Later this month, the volunteer will stop taking the antiretroviral drugs he was taking to keep the virus at undetectable levels. Then investigators will wait 12 weeks to see if the virus rebounds. Otherwise, they will consider the experience a success. “What we’re trying to do is bring the cell back to a near-normal state,” says Daniel Dornbusch, CEO of Excision BioTherapeutics, the San Francisco-based biotech company leading the trial.
The HIV virus attacks the body’s immune cells called CD4 cells and hijacks their machinery to reproduce. But some HIV-infected cells can lie dormant, sometimes for years, and not actively produce new copies of the virus. These so-called reservoirs are a major obstacle to curing HIV.
“HIV is a tough enemy to fight because it’s able to insert itself into our own DNA, and it’s also able to shut down and reactivate itself at different times in a person’s life,” says Jonathan Li, physician 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 do it without damaging vital CD4 cells — has proven difficult, 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 eliminate HIV for good.
Crispr is used in several other studies to treat a handful of conditions resulting from genetic mutations. In these cases, scientists are using Crispr to edit people’s own cells. But for the HIV trial, the Excision researchers are turning the gene-editing tool against the virus. The Crispr infusion contains gene-editing molecules that target two regions of the HIV genome important for viral replication. The virus can only reproduce if it is fully intact, so Crispr disrupts this process by cutting off pieces of the genome.
In 2019, researchers from Temple University and the University of Nebraska found that using Crispr to delete these 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.
