In all areas of life, immune defenses thwart invading viruses by making their replication impossible. The best-known CRISPR systems target the DNA of invading pathogens and cut it to disable and modify genes, thereby preventing infections at the passage (cellular) level.
Ryan Jackson, a chemist at Utah State University, and his students are studying two lesser-known CRISPR (clustered regularly interspaced short palindromic repeats) systems, known as Cas12a2 and Cas12a3. Unlike the better-known CRISPR-Cas9, which uses a guide RNA to locate a specific DNA sequence, Cas12a2 and Cas12a3 target RNA directly.
We are very focused on fundamental research aimed at understanding the structure and function of the CRISPR systems we study and helping researchers around the world overcome bottlenecks that allow them to pursue therapeutic applications.
Jackson, R. Gaurth Hansen, associate professor in the USU Department of Chemistry and Biochemistry
Along with doctoral student Kadin Crosby and master’s student Bamidele Filani, Jackson, along with collaborators in Europe, report new findings on CRISPR-Cas12a3 in the January 7, 2026 issue of the journal. Nature. These findings could lead to more efficient and accurate diagnostic tools to quickly detect COVID, influenza and RSV infections, individually or in combination, with a single test, in a single patient.
Jackson and his team are learning more about the distinctive features of Cas12a2 and Cas12a3.
“Instead of making a single break in the bound target, as Cas9 does with DNA, binding of the RNA target by Cas12a2 and Cas12a3 changes the shape of a protein in a way that activates it to cut another nucleic acid target again and again,” he says. “When activated, Cas12a2 indiscriminately cleaves DNA, destroying all viral DNA, but also collaterally killing the host cell. In contrast, Cas12a3 cleaves transfer ribonucleic acids, called tRNAs, interrupting the production of viral proteins, while sparing host cell DNA. »
This latter capacity allows Cas12a3 to target tRNA very precisely. Jackson and his team are trying to harness this ability to detect and target specific pathogens.
“tRNA is the keystone of protein synthesis,” Jackson explains. “It functions as a translation device that can read the RNA code and act as a molecular bridge to connect that code to the correct amino acid to enable protein production. »
Cas12a3 has the ability to disable the translation capacity of tRNA.
“Cas12a3 can stop protein production by cutting a specific region of the tRNA, called the ‘tail,’ which contains the amino acid,” he says. “This is a very powerful and precise way to stop a pathogen, including a virus, from replicating in a cell, without damaging the cell’s DNA. »
Jackson says Cas12a3’s ability to cleave tRNA tails is a recently discovered CRISPR immune response.
“We think being able to stop an invading pathogen while leaving the DNA unchanged could be a therapeutic breakthrough,” he says. “By studying these systems, we are also discovering the enormous functional diversity of these bacterial defense mechanisms. »
Jackson adds that Crosby and Filani played key roles in discovering and defining the specific functions of Cas12a3 and determining its ability to function as a diagnostic tool.
Study collaborators include Chase Beisel of the Helmholtz Institute for RNA Infection Research in Würzburg and Dirk Heinz of the Helmholtz Center for Infection Research in Braunschweig, as well as researchers from the Jagiellonian University of Poland, the University of Strasbourg in France, the Freie University of Germany, the Robert Koch Institute in Germany, the University of Veterinary Medicine of Austria, and the Institute of technologies from Austria.
Jackson and his students’ research is supported by the R. Gaurth Hansen family and the National Institutes of Health.
