Using a high-resolution imaging technique called cryo-EM, the team discovered that when this protein, called Cas12a2, binds to specific sequences in the genetic material of a potentially dangerous virus called target RNA, the side of Cas12a2 moves outward. reveal an active area similar to a rotating open valve blade. The active site then begins to indiscriminately cut any genetic material it comes in contact with. The researchers discovered that with a single mutation in the Cas12a2 protein, the active site degrades only single-stranded DNA – particularly useful in developing new diagnostics tailored to any of the many viruses.

A test based on this technology could theoretically combine the best features of PCR-based tests that detect genetic material from the virus (high sensitivity, high accuracy, and the ability to detect active infection) with the best features of rapid at-home diagnostic tests. (cheap to produce without requiring special lab equipment). It can also easily adapt to any new RNA virus.

“If a new virus comes out tomorrow, all you have to do is find its genome and then change the guide RNA in your test, and you’ll have a test against it,” said David Taylor, associate professor of molecular biosciences. at the University of Texas at Austin and co-author of the new study.

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Such a diagnosis would still require separate work and would likely involve collecting a saliva or nasal sample from the patient to mix with the team’s modified Cas12a2 protein, a piece of guide RNA that acts as a miracle to identify a specific virus, and a fluorescent probe. its single-stranded DNA is designed to burn when cut.

“Cas12a2 basically grabs both ends of the DNA double helix and twists it very tightly,” said Jack Bravo, a postdoctoral researcher at UT Austin and first author of the paper. “And so the helix in the middle unwinds, allowing this active site to destroy bits of DNA that have become single-stranded. That’s what sets Cas12a2 apart from all other DNA targeting systems.”

Source: Eurekalert

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