Editing HIV out of our genome with CRISPR

UMMS scientists seek ways to use powerful gene editing tool to excise latent HIV virus

VIDEO:Scot Wolfe, Ph.D., associate professor of molecular, cell and cancer biology, and Jeremy Luban, M.D., the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass... view more

WORCESTER, MA -The virus that causes AIDS is an efficient and crafty retrovirus. Once HIV inserts its DNA into the genome of its host cells, it has a long incubation period, and can remain dormant and hidden for years. And while physicians can mix and match a cocktail from a host of antiretroviral drugs to keep the virus in check, the virus can reactivate if treatment is stopped.

In an attempt to render latent HIV completely harmless, researchers at the University of Massachusetts Medical School are using Cas9/CRISPR, a powerful gene editing tool, to develop a novel technology that can potentially cut the DNA of the latent virus out of an infected cell.

"On the simplest level we're employing a very precise pair of scissors to go in and clip out all, or part of, the HIV genome and reattached the severed ends of the human genome," said principal co-investigator Scot Wolfe, PhD, associate professor of molecular, cell and cancer biology at UMass Medical School. "If we could do that, the hope is that this would be a step on the road to getting a functional cure for HIV."

A component of the immune system found in normal bacteria, in its natural state CRISPR protects bacteria from viral invasion. Since its discovery, researchers have been furiously finding ways to program this system to quickly and selectively edit specific genetic sequences for study.

For all its versatility, applications for the CRISPR system remain confined to the lab. Despite recent advances showing that Cas9/CRISPR can edit HIV from an infected cell in culture, this technique remains too imprecise to be used clinically because of its tendency to cut into random regions of the genome, producing deleterious, off-target effects.

To improve the fidelity and precision of the Cas9/CRISPR gene editing system for this project, Wolfe has proposed fusing it with an additional domain that improves its specificity. This would conceivably allow the CRISPR system to edit out only the HIV DNA without the potential for stray cuts in the human genome.

The other hurdle to using current Cas9/CRISPR technology against HIV is that while researchers have some notions where the virus might be hiding, they still don't know how to find the virus in latently infected cells.

"Cells that are infected with HIV are permanent carriers of the viral genome. They are a kind of time bomb that can reactive at any time if a patient stops taking their antiretroviral treatment," said principal co-investigator Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass Medical School. "In order to attack the virus in its latent state, we really need to understand where the virus lives and what it needs to survive."

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Editing HIV out of our genome with CRISPR