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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

The dark new reality in Congress

National Guard troops keep watch at security fencing. Photo: Kent Nishimura/Los Angeles Times via Getty Images

This is how bad things are for elected officials and others working in a post-insurrection Congress:

  • Rep. Norma Torres (D-Calif.) said she had a panic attack while grocery shopping back home.
  • Rep. Jim McGovern (D-Mass.) said police may also have to be at his constituent meetings.
  • Rep. Adam Kinzinger (R-Ill.) told a podcaster he brought a gun to his office on Capitol Hill on Jan. 6 because he anticipated trouble with the proceedings that day.
Off the Rails

Episode 3: Descent into madness

Photo illustration: Sarah Grillo/Axios. Photos: Tom Williams/CQ-Roll Call, Chip Somodevilla/Getty Images

Beginning on election night 2020 and continuing through his final days in office, Donald Trump unraveled and dragged America with him, to the point that his followers sacked the U.S. Capitol with two weeks left in his term. This Axios series takes you inside the collapse of a president.

Episode 3: The conspiracy goes too far. Trump's outside lawyers plot to seize voting machines and spin theories about communists, spies and computer software.

President Trump was sitting in the Oval Office one day in late November when a call came in from lawyer Sidney Powell. "Ugh, Sidney," he told the staff in the room before he picked up. "She's getting a little crazy, isn't she? She's really gotta tone it down. No one believes this stuff. It's just too much."

Convicts turn to D.C. fixers for Trump pardons

Trump confidante Matt Schlapp interviews Jared Kushner last February. Schlapp is seeking a pardon for a biotech executive. Photo: Samuel Corum/Getty Images

A flood of convicted criminals has retained lobbyists since November’s presidential election to press President Trump for pardons or commutations before he leaves office.

What we're hearing: Among them is Nickie Lum Davis, a Hawaii woman who pleaded guilty last year to abetting an illicit foreign lobbying campaign on behalf of fugitive Malaysian businessman Jho Low. Trump confidante Matt Schlapp also is seeking a pardon for a former biopharmaceutical executive convicted of fraud less than two months ago.