RNA-triggered cell killing with CRISPR-Cas12a2
- Nature. 2026 Jul;655(8121):230-239. doi: 10.1038/s41586-026-10466-y.
- 1. Akribion Therapeutics GmbH, Zwingenberg, Germany. [email protected].
- 2. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
- 3. Department of Chemistry and Biochemistry, Utah State University, Logan, UT, USA.
- 4. Akribion Therapeutics GmbH, Zwingenberg, Germany.
- 5. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
- 6. BRAIN Biotech AG, Zwingenberg, Germany.
- 7. Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.
- 8. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
- 9. Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
- 10. Department of Chemistry and Biochemistry, Utah State University, Logan, UT, USA. [email protected].
- 11. Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany. [email protected].
- 12. Medical Faculty, University of Würzburg, Würzburg, Germany. [email protected].
- 13. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA. [email protected].
- # Contributed equally.
Selectively eradicating target cells on the basis of their genetic or transcriptional identity remains important in basic research, medicine, biotechnology and agriculture1-3. For applications involving bacteria, CRISPR nucleases offer promising options due to their ability to enact RNA-guided counterselection4-7; however, using these same nucleases for counterselection in eukaryotes has proven much more restrictive8-14. Here we show that Cas12a2, a recently discovered type V CRISPR Nuclease, exhibits RNA-triggered DNA shredding15,16, and enables programmable and sequence-specific elimination of yeast and human cells expressing a target transcript. Triggering Cas12a2 elicits rampant double-stranded DNA breaks in trans, leading to cell death. Cell killing can be activated by a wide range of target transcripts, with no observed off-target activation. Leveraging this approach, we selectively eliminate cells that harbour human papillomavirus, cells that failed to undergo Gene Editing, or cells that encode a prevalent oncogenic point mutation in KRAS. These findings expand the CRISPR toolbox to allow the selective elimination of eukaryotic cells on the basis of their transcriptional profile.