Taming CasRx: When delivery becomes part of the safety mechanism

RNA-targeting CRISPR systems have transformed the ability to manipulate gene expression without permanently altering the genome. Among them, Cas13 effectors offer programmable RNA knockdown with considerable therapeutic potential, but their biology poses an unusual safety challenge: target recognition can activate collateral cleavage of non-target RNAs. This phenomenon has been demonstrated in mammalian cells and appears to depend on the Cas13 ortholog, target abundance, cellular context, and expression level.