Cas9

Cas9 is the molecular scissors of the most popular CRISPR system. On its own it does nothing useful — it is like a guided drone without a destination. Loaded with a guide RNA, it becomes a homing device: it scans the genome, finds the sequence that matches its guide, and snips the DNA there.

Cas9 is an enzyme called a nuclease, originally from the bacterium Streptococcus pyogenes. It first checks for a short signal called a protospacer adjacent motif (PAM) right next to the target; only then does it unwind the DNA, let the guide RNA pair with one strand, and use two cutting domains to break both strands of the double helix, producing a double-strand break.

By disabling one or both of its cutting domains, scientists make modified versions: a “nickase” that cuts only one strand, or a “dead” Cas9 (dCas9) that binds DNA without cutting and can carry other tools to switch genes on or off. So Cas9 is best thought of as a programmable DNA-binding platform, not merely a pair of scissors.