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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

Updated 33 mins ago - Axios Twin Cities

In photos: Twin Cities on edge after Daunte Wright shooting

Police officers form a line as they face off with demonstrators protesting the death of Daunte Wright outside the Brooklyn Center police station on April 12 in Brooklyn Center, Minnesota. Photo by Scott Olson/Getty Images

There were tense scenes in the Twin Cities suburb of Brooklyn Center Monday night, after demonstrators defied a 7 p.m. curfew to protest for a second night the fatal police shooting of Daunte Wright.

The big picture: The curfew was announced following a night of protests and unrest over the killing of Wright, 20, during a traffic stop Sunday. Following peaceful protests and a daytime vigil, police again deployed tear gas during clashes with protesters Monday night, according to reporters on the scene.

Japan to release Fukushima water into sea

People near storage tanks for radioactive water at the Fukushima Dai-ichi nuclear power plant in Okuma, Fukushima Prefecture, Japan, in 2020. Photo: Tomohiro Ohsumi/Getty Images

Japan's government on Tuesday announced plans to release more than 1 million metric tons of contaminated water from the destroyed Fukushima nuclear plant into the Pacific Ocean following a treatment process.

Why it matters: While the Biden administration has said Japan appears to have met globally accepted nuclear safety standards, officials in South Korea, China and Taiwan, local residents, those in the fishing industry and green groups oppose the plans, due to begin in about two years, per the Guardian.

In photos: Life along the U.S.-Mexico border

Children at the border of the Puerto de Anapra colonia of Ciudad Juárez, Mexico, hang on a border fence and look to Sunland Park, N.M. Photo: Russell Contreras/Axios

Axios traveled to McAllen and El Paso, Texas, and Ciudad Juárez, Mexico, to see how the communities are responding to an increase of migrants from Central America.

Of note: The region in South and West Texas are among the poorest in the nation and rarely are the regions covered in depth beyond the soundbites and press conference. Axios reporters Stef Kight and Russell Contreras walked the streets of McAllen, El Paso, Texas, and Ciudad Juárez to record images that struck them.