Fig. 4

Paired Cas9 nickase and FokI-dCas9 systems. Alternative Cas9 proteins can decrease off-target effects. a Two nickases are required to make a double-strand break, increasing the gRNA requirement and length of target sequence. b A catalytically dead Cas9 is paired to a Fok1 nuclease, also resulting in an increased length of target sequence for enhanced targeting specificity