A bold effort to cure HIV—using Crispr

3D illustration of HIV.
Zoom / 3D illustration of HIV.

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 from its cells. For an hour, he was attached to an intravenous bag that pumped the experimental treatment directly into his bloodstream. The one-time injection is designed to transfer gene-editing tools into infected man’s cells to remove the virus.

Later this month, the volunteer will stop taking the antiretroviral medications he uses to keep the virus at undetectable levels. Then, investigators will wait 12 weeks to see if the virus has rebounded. If not, they will consider the experiment a success. “What we’re trying to do is return the cell to a near-normal state,” says Daniel Dornbusch, CEO of Excision BioTherapeutics, the San Francisco-based biotechnology company that is running the experiment.

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HIV attacks the body’s immune cells called CD4 cells and hijacks their organs to make copies of themselves. But some HIV-infected cells can lie dormant — sometimes for years — and not effectively produce new virus copies. These so-called reservoirs are a major barrier to HIV treatment.

“HIV is a difficult enemy to fight because it is able to insert itself into our DNA, and it is also able to silence and reactivate at various stages of a person’s life,” says Jonathan Lee, MD, a physician at Brigham and Women’s and HIV Hospital. A Harvard researcher who was not involved in the Crispr trial. Figuring out how to target these reservoirs — and do so without harming vital CD4 cells — has proven challenging, Lee says.

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While antiretroviral drugs can stop virus replication and remove the virus from the blood, they cannot reach these reservoirs, so people have to take the drugs every day for the rest of their lives. But Excision BioTherapeutics hopes Crispr will eliminate HIV for good.

CRISPR is used in many other studies to treat a small number of conditions that arise from genetic mutations. In these cases, scientists use CRISPR to modify human cells. But for the HIV trial, Excision researchers are turning a gene-editing tool against the virus. Crispr injection contains gene-editing molecules that target two regions of the HIV genome that are important for viral replication. The virus can only replicate if it is completely healthy, so Crispr disrupts this process by cutting parts of the genome.

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In 2019, researchers at 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, Temple’s group also showed that this approach safely removed viral DNA from macaques infected with SIV, the monkey’s version of HIV.

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