A non-rational approach to optimized targeting of CRISPR-Cas9 complexes

In this issue of Cell Chemical Biology, Bush et al.1 report an in vitro selection method for optimizing CRISPR-Cas9 single-guide RNAs. This approach may be useful in targeting previously intractable genomic se-quences. The results also provide insights into which positions in single-guide RNAs are most amenable to modification.