New CRISPR system selectively destroys cancer cells
· News-MedicalAmong the challenges in treating disease, including cancer, is wiping out malignancies, infection, contaminants or other pathologies, without destroying healthy tissue.
"This is a holy grail of medicine and other sciences," says Utah State University biochemist Ryan Jackson who, with USU doctoral candidate Kadin Crosby and colleagues from other institutions, reports a breakthrough discovery about CRISPR-Cas12a2 in the May 6, 2026, online issue of the journal Nature.
Collaborating institutions on the research, which was supported by the National Institutes of Health and the R. Gaurth Hansen Family, include the University of Utah, along with the Helmholtz Institute for RNA-based Infection Research and the University of Würzburg in Germany.
CRISPR-Cas12a2 is among the newly discovered and obscure CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) immune defense systems Jackson and his students study. Unlike the better-known CRISPR system Cas9, which uses a guide RNA (Ribonucleic acid) to bind complementary DNA, Cas12a2 uses a guide RNA to bind complementary RNA.
"In contrast to activated Cas9, which makes a single precise cut in the bound DNA, RNA target-activated Cas12a2 shreds all DNA it encounters, effectively killing the cell," says Jackson, R. Gaurth Hansen Associate Professor in USU's Department of Chemistry and Biochemistry and co-corresponding author on the paper.
However, if the guide RNA is not a perfect complement to the RNA target, he says, Cas12a2 does not activate and the cell is spared.
"We demonstrate Cas12a2 can selectively kill cells containing a single-point mutant that causes cancer, while leaving cells without the mutant unaffected, with no observable side effects," says Crosby, co-first author on the paper. "In mice, our therapy reduced tumor volume by about 50 percent after a single treatment."
Yang Liu, Assistant Professor of Biochemistry at University of Utah Health and co-corresponding author, says Cas12a2 has a particular focus.
"Its goal is not to correct anything," Liu says. "Instead, it's to destroy anything it sees. The enzyme that we're working with is extremely specific. It does not touch healthy cells. That was striking to us."
Use of Cas12a2 for human therapies will require thorough research and testing in humans, but the researchers are optimistic their findings are a step in the right direction.
"Because Cas12a2 can be programmed with a guide RNA to target any RNA sequence, and it shows little to no off-targeting, we believe we have discovered a way to selectively kill cells across all of biology," Jackson says. "We show it can be used to enrich for gene editing, and to selectively kill cells harboring virus genes, and to kill cells with acquired mutations. We envision this technology will transform science, agriculture and medicine in ways previously unavailable."
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