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.