Key Details
Researchers programmed CRISPR-Cas12a, an RNA-guided nuclease with trans-nucleolytic cleavage activities, to selectively kill cancer cells.
The approach targets cancer-specific transcripts, limiting cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death.
This method enables targeting of undruggable mutations, such as those in the p53 tumor suppressor protein, which lacks defined drug-binding pockets.
Background
Genetic mutations driving cancer often affect tumor suppressor proteins like p53, altered in ~40-50% of cases. Current therapies fail to target most such mutations due to the lack of defined drug-binding pockets and challenges in restoring endogenous function.
Significance
Transcript-activated chromatin shredding provides a new approach for precision disease treatments targeting undruggable targets.