RNA-triggered cell killing with CRISPR-Cas12a2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42092133.
- Also identified by DOI 10.1038/s41586-026-10466-y.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Selectively eradicating target cells on the basis of their genetic or transcriptional identity remains important in basic research, medicine, biotechnology and agriculture<sup>1-3</sup>. For applications involving bacteria, CRISPR nucleases offer promising options due to their ability to enact RNA-guided counterselection<sup>4-7</sup>; however, using these same nucleases for counterselection in eukaryotes has proven much more restrictive<sup>8-14</sup>. Here we show that Cas12a2, a recently discovered type V CRISPR nuclease, exhibits RNA-triggered DNA shredding<sup>15,16</sup>, 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.