Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants

A PAMless base editor CRISPR-Cas DNA base editing typically requires a specific motif for targeting known as a protospacer-adjacent motif (PAM). This requirement limits the sequences within a genome that can be targeted. Walton et al. engineered specific variants of the Streptococcus pyogenes Cas9 enzyme named SpG and SpRY that could recognize and edit a wider array of PAMs. Using SpRY, the authors were able to correct previously uneditable mutations associated with human disease. Although off-target effects were observed for these engineered Cas enzymes at levels similar to those of the wild-type enzyme, depending on the context, these engineered enzymes widen the potential applications of precision genome editing. Science , this issue p. 290