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A researcher performs a CRISPR-Cas9 process. Credit: Gregor Fischer/picture alliance via Getty Images

Researchers say they've discovered why the enzyme Cas12a may be safer and more precise than Cas9 in most cases to use with the gene editing tool, CRISPR, according to a study published today in Molecular Cell .

Why it matters: Cas9 is the first-discovered and most popular enzyme used by the CRISPR technology, but it has been known to have safety concerns. It sometimes unsafely targets the wrong gene or even deletes sections of the genome. However, Cas12a may be safer because it discriminates more strongly against mismatches than Cas9, the scientists say.

"Why don't we start with the best protein that nature has given us [Cas12a] and improve on that."
— Ilya Finkelstein, study author, assistant professor of molecular biology, University of Texas-Austin

Background: CRISPR technology can use different proteins to cut the DNA, and there is a lot of research looking into other alterations of Cas9 to improve it, as well as different proteins, like Cas12a. Both Cas9 and Cas12a rely on a 20-letter guide (or a 20-nucleotide RNA) to identify the DNA targeted for edits, but their processes are slightly different.

Some differences, per The Broad Institute:

  • Cas9 uses two small RNAs and cuts both strands of the target DNA at the same place, creating "blunt edges" that can undergo mutation when the strands repair themselves. (Although, FierceBiotech points out there are efforts to make Cas9 safer).
  • Cas12 uses a single RNA and is smaller, which can make it easier to enter cells.

What they found: Researchers from UT-Austin wanted to confirm Cas12 was more precise and to determine why. They found that Cas9 starts binding to its DNA target after reading only the 7 or 8 letters of the 20-letter code. However, Cas12a appears to read up to 18 of the letters before it binds fully, and if it finds a mismatch, it will fall off before it binds.

  • This is key, Finkelstein tells Axios, because a person can have DNA circulating around their body that have very similar letters, which may cause editing of the wrong DNA. Eventually, they hope to get Cas12a to match all 20 letters, he says.
  • However, he adds, there are also some disadvantages to using Cas12a over Cas9. For one thing, Cas12a tends to remain tightly associated with one of the two DNA molecules after the genome is cut, and they don’t know how this would impact gene editing and repair.
  • He says Cas9 acts like "superglue" while Cas12a is more similar to "velcro."

What's next: More trials are needed, and research to make it even more precise. Finkelstein says there will be "thousands" of Cas12a and Cas9 enzymes produced as scientists seek to improve the proteins, including by his laboratory, because "it's important to expand our genome editing toolkit."

"For the first time in the history of humanity, we now have access to tools that will let us control our genetic future."
— Ilya Finkelstein, University of Texas-Austin

Go deeper:

Go deeper

Scoop: Trump's new social network quietly courting influencers

Illustration: Lazaro Gamio/Axios

Former President Trump’s elusive new social media network Truth Social — which plans to go public — is reaching out to internet influencers asking them to “reserve their spots” for when it launches in February or March.

Why it matters: The outreach doesn’t mention Trump’s name or affiliation. Some influencers suggest that could be a ploy to enlist their support without realizing the affiliation.

Ben Geman, author of Generate
44 mins ago - Energy & Environment

The electric aviation market is buzzing

Illustration: Megan Robinson/Axios

Boeing's $450 million investment in the autonomous electric air taxi startup Wisk is the latest sign of capital pouring into tech that could one day transform urban and regional mobility and curb carbon emissions.

Catch up fast: The aviation giant's latest funding for Wisk will help the California-based company develop the latest version of its electric vertical takeoff and landing (eVTOL) aircraft.

The SAT is going digital

A practice SAT. Photo: Alex Garcia/Los Angeles Times via Getty Images

The College Board announced Tuesday that the SAT will be delivered digitally in the U.S. in 2024.

Why it matters: The College Board said it's seeking to make the SAT "more relevant," as some colleges start to ditch the college admissions exam altogether.