RNA-triggered cell killing with CRISPR–Cas12a2
Researchers have demonstrated that the CRISPR nuclease Cas12a2 enables RNA-triggered, sequence-specific elimination of eukaryotic cells. Published in Nature, this study addresses a significant limitation in using CRISPR technologies for counterselection in eukaryotes, where traditional nucleases like Cas9 often fail to induce cell death due to efficient DNA repair mechanisms. Upon recognizing a specific target transcript, Cas12a2 unleashes indiscriminate double-stranded DNA shredding activity across the genome, leading to rampant DNA damage and subsequent cell death. The team successfully applied this method to selectively kill yeast and human cells expressing target transcripts, including those infected with human papillomavirus, cells that failed gene editing, and cells harboring oncogenic KRAS mutations. Notably, the process showed no observed off-target activation. This breakthrough expands the CRISPR toolbox, offering a programmable approach to eradicate cells based on their transcriptional profiles. It holds substantial promise for basic research, medicine, biotechnology, and agriculture, particularly for targeting difficult-to-drug conditions such as non-coding mutations or complex disease etiologies.
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RNA-triggered cell killing with CRISPR–Cas12a2
Researchers have demonstrated that the CRISPR nuclease Cas12a2 enables RNA-triggered, sequence-specific elimination of eukaryotic cells. Published in Nature, this study addresses a significant limitation in using CRISPR technologies for counterselection in eukaryotes, where traditional nucleases like Cas9 often fail to induce cell death due to efficient DNA repair mechanisms. Upon recognizing a specific target transcript, Cas12a2 unleashes indiscriminate double-stranded DNA shredding activity across the genome, leading to rampant DNA damage and subsequent cell death. The team successfully applied this method to selectively kill yeast and human cells expressing target transcripts, including those infected with human papillomavirus, cells that failed gene editing, and cells harboring oncogenic KRAS mutations. Notably, the process showed no observed off-target activation. This breakthrough expands the CRISPR toolbox, offering a programmable approach to eradicate cells based on their transcriptional profiles. It holds substantial promise for basic research, medicine, biotechnology, and agriculture, particularly for targeting difficult-to-drug conditions such as non-coding mutations or complex disease etiologies.
Nature