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Molecular Scissors Could Help Keep Some Viral Illnesses At Bay

Susanna M. Hamilton
Broad Communications

It's not easy to treat viral infections. Just ask anyone with a bad cold or a case of the flu.

But scientists in Massachusetts think they may have a new way to stop viruses from making people sick by using what amounts to a pair of molecular scissors, known as CRISPR.

It's a gene editing tool based on a molecule that occurs naturally in microorganisms.

CRISPR comes in many "flavors" that perform a variety of functions inside cells. The Cas9 flavor has been widely used as a tool for editing DNA inside cells. It's already shown promise for medical therapies such as treating sickle cell disease.

What's different is that the antiviral approach researchers at the Broad Institute in Cambridge are using involves a form of CRISPR called Cas13 that targets specific regions of RNA, not DNA.

RNA is a chemical cousin of DNA. Many viruses, including flu and Zika, package their genetic instructions in RNA instead of DNA.

When a virus infects a cell in our bodies, it hijacks the cell's molecular machinery to make copies of itself. Those new viruses can go on to spread the infection through your body.

So for therapy, "we need to be able to cut the virus at a fast enough rate to slow down replication or to stop replication from happening," says Cameron Myhrvold, a postdoc at the Broad Institute.

Finding the right target is key. There's a lot of RNA inside cells that is necessary for the cell to survive, so it's important to find an RNA target that's unique to the virus you're trying to control.

Myhrvold says RNA viruses are particularly difficult to control because they are a bit like shape-shifters: They tend to change their genetic sequences when you try to pin them down. That's one of the reasons people need a new flu vaccine each year.

Understanding how the virus changes in response to Cas13 treatment should be informative.

"That could potentially teach us about what parts of the virus are particularly important for its function," says Catherine Freije, a doctoral student at the Broad Institute. And that in turn will show the best places to target the virus in order to disable it.

So far, Freije and Myhrvold say they've only shown their antiviral treatment works in cells.

But Pardis Sabeti, head of the lab they work in, is bullish about using the CRISPR Cas13 system to treat viral infections in people.

"There's still a bunch of things we want to work out, but we feel pretty confident that this will work as a therapy if it can be delivered in the right way," Sabeti says.

By delivering, she means getting the CRISPR Cas13 tool into the right cells inside an infected patient.

Since CRSIPR Cas13 specifically targets RNA, it will only be useful for illnesses caused by RNA.

Janice Chen says researchers are now finding a variety of CRISPRs with different properties. Chen is chief research officer at Mammoth Biosciences, a company that hopes to capitalize on CRISPR technology.

"Having a broader CRISPR toolbox is really important to figure out what is the specific need for any given application," Chen says.

Progress in building that toolbox has proceeded quite quickly. After all, it's only been six years since scientists first became aware of how powerful a tool CRISPR could be.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

Joe Palca is a science correspondent for NPR. Since joining NPR in 1992, Palca has covered a range of science topics — everything from biomedical research to astronomy. He is currently focused on the eponymous series, "Joe's Big Idea." Stories in the series explore the minds and motivations of scientists and inventors. Palca is also the founder of NPR Scicommers – A science communication collective.

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