2. Academic Validation
  3. RNA-triggered cell killing with CRISPR-Cas12a2

RNA-triggered cell killing with CRISPR-Cas12a2

  • Nature. 2026 Jul;655(8121):230-239. doi: 10.1038/s41586-026-10466-y.
Paul Scholz # 1,  Jared Thompson # 2,  Kadin T Crosby # 3,  Torsten Fauth 4,  Nathan M Krah 2 5,  Grant Schlauderaff 2,  Robin Back 4,  Zachary A Berkheimer 2,  Alivia Jolley 2,  Dirk Sombroek 4,  Rebekka Medert 4,  Christian Zurek 6,  Oleg Dmytrenko 7,  Emily Wilson 8,  Friso T Schut 7,  Jared Rutter 2 9,  Xiaoyang Zhang 8,  Michael Krohn 4,  Ryan N Jackson 10,  Chase L Beisel 11 12,  Yang Liu 13
Affiliations

Affiliations

  • 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.
PMID: 42092133 DOI: 10.1038/s41586-026-10466-y
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-114277
    99.70%, KRAS G12C Inhibitor
    Ras