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Newly discovered anti-CRISPR protein gives viruses a leg up against bacteria

CRISPR-Cas systems, known for their powerful gene-editing applications, are bacteria’s version of an immune system. When infected with a virus, bacteria use this piece of molecular machinery to form a memory of the intruder’s genetic sequence so that, the next time that same virus attacks, CRISPR-Cas will quickly recognize and destroy it.

But viruses too have molecular tricks up their sleeves, allowing some of them to combat CRISPR defenses. Recently, Alexander Meeske, a postdoctoral fellow in Luciano Marraffini’s lab, discovered such a viral anti-CRISPR system that might be the most potent one yet described. It acts on a system called CRISPR-Cas13 that, unlike most other CRISPR systems, destroys a virus’s RNA rather than its DNA.

Collaborating with a team at Memorial Sloan Kettering Cancer Center, the researchers found that some viruses produce a protein called AcrVIA1, which shuts down the bacterial immune system by binding to a strategic place in the CRISPR-Cas13 machinery, preventing it from recognizing the viral RNA. Their experiments revealed AcrVIA1 to be exceptionally powerful: Unlike other known anti-CRISPR proteins, it doesn’t seem to rely on multiple viral infections to succeed. Marraffini and colleagues found that even a single dose of AcrVIA1 could completely dismantle a bacterium’s immunity.

“This protein could be a really useful component when editing genes using this specific CRISPR-Cas system,” says Marraffini.

Luciano Marraffini

Luciano Marraffini
Investigator, Howard Hughes Medical Institute
Laboratory of Bacteriology

Related publication

A phage-encoded anti-CRISPR enables complete evasion of type VI-A CRISPR-Cas immunity
Alexander J. Meeske, Ning Jia, Alice K. Cassel, Albina Kozlova, Jingqiu Liao, Martin Wiedmann, Dinshaw J. Patel, and Luciano A. Marraffini

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