Since the discovery of RNA-programmable nucleases from the
prokaryotic adaptive immune system CRISPR–Cas, these
proteins have seen rapid and widespread adoption for
biotechnological and clinical research. A recently discovered
system, CRISPR–Cas13, uses CRISPR RNA guides to target
RNA. Interestingly, RNA targeting by Cas13 results in cleavage
of both target RNA and bystander RNA. This feature has been
used to develop innovative diagnostic tools for the detection of
specific RNAs. Unlike in vitro detection of RNA using collateral
RNA cleavage, however, initial studies of mammalian cells only
revealed highly specific target RNA-knockdown activity.
Although these findings have been confirmed subsequently,
several recent publications do report Cas13-mediated toxicity
and collateral RNA cleavage when using Cas13 in eukaryotes.
Here, we review these conflicting observations and discuss its
potential molecular basis.

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