Researchers at Utah State University have unveiled two new CRISPR systems that target RNA rather than DNA, revealing potential breakthroughs in cancer treatment and viral diagnostics.
The studies, led by chemist Ryan Jackson and published in the journal Nature, detail the mechanisms of Cas12a2 and Cas12a3—two distinct immune defense systems that operate in fundamentally different ways from the well-known CRISPR-Cas9.
The Studies
A study published in the May 6, 2026, online issue of Nature details the CRISPR-Cas12a2 system. The research was conducted by Jackson, doctoral candidate Kadin Crosby, and colleagues from the University of Utah, the Helmholtz Institute for RNA-based Infection Research, and the University of Würzburg.
A second study, published in the January 7, 2026, issue of Nature, reports findings on the CRISPR-Cas12a3 system. Jackson, Crosby, and master's student Bamidele Filani contributed to this research, alongside collaborators from multiple European institutions, including the Helmholtz Institute for RNA-based Infection Research, the Helmholtz Center for Infection Research in Germany, Jagiellonian University in Poland, the University of Strasbourg in France, Freie University in Germany, the Robert Koch Institute in Germany, the University of Veterinary Medicine Austria, and the Institute of Science and Technology Austria.
Mechanisms of Action
Both Cas12a2 and Cas12a3 target RNA, unlike the DNA-targeting CRISPR-Cas9. When activated by binding a specific RNA target, both systems undergo a conformational change that triggers them to repeatedly cleave other nucleic acid targets. However, their specific actions differ dramatically.
Cas12a2: Indiscriminate DNA Destruction
When activated by binding a specific RNA target, Cas12a2 indiscriminately cleaves all DNA it encounters.
This process can destroy viral DNA, but it also results in the death of the host cell. The system acts as a powerful, all-or-nothing immune response.
Cas12a3: Targeted tRNA Disruption
Upon activation, Cas12a3 specifically cleaves transfer ribonucleic acids (tRNAs), halting viral protein production while preserving the host cell's DNA.
This is a newly identified CRISPR immune response. By severing the 'tail' region of tRNAs that carries amino acids, Cas12a3 disables their translation function. This stops viral replication without destroying the host cell's genetic material.
Potential Applications
Cancer Treatment
The research on Cas12a2 indicates it can be programmed to target specific RNA sequences. Crucially, the enzyme's activation requires a perfect match between the guide RNA and the target RNA; imperfect matches do not trigger cell death.
Researchers state that Cas12a2 can selectively kill cells containing a single-point mutation that causes cancer.
In a study on mice, a single treatment with Cas12a2 reduced tumor volume by approximately 50%. The researchers reported no observable side effects in the mice. They caution, however, that use for human therapies will require thorough testing in humans.
Viral Diagnostics and Therapy
The precise nature of Cas12a3's tRNA-targeting ability is being investigated for several applications:
- Diagnostic tools capable of detecting infections such as COVID, influenza, and RSV.
- Potential therapeutic uses based on the mechanism of inhibiting pathogen replication without damaging host cell DNA.
Funding
Funding for the research was provided by the R. Gaurth Hansen Family and the National Institutes of Health.