The three main CRISPR–Cas Types that have been successfully used to edit phages. Shown are protein and nucleic acid requirements for crRNA biogenesis and interference steps in representative CRISPR–Cas systems: Type I-E from E. coli (A), Type II-A from S. pyogenes (B), and Type III-A from S. epidermidis (C). Numbered ovals represent corresponding Cas proteins, and “s” represents one or more copies of a small subunit specific to each subtype. Black scissors represent cleavage points made by the overlapping protein subunit, while grey scissors represent cleavage events catalyzed by non-Cas and/or unknown nucleases. For Type I and II systems, the PAM and seed sequences are represented by red and orange rectangles, respectively. For Type III systems, the crRNA tag is represented by a black square, and the opposing anti-tag is shown as a white square. cOA, cyclic oligoadenylates.