Supplementary Figure 11: eA3A retains high genome-wide fidelity when used with VRQR SpCas9.

Off-target editing frequencies of two gRNAs targeted to PPP1R12C VRQR site 1 or 3 with BE3 or eA3A-BE3. Percentage edits represent the sum of all edited Cs in the editing window and represent the mean of three biological replicates with error bars representing SEMs. Intended target sequence is shown at the top of each graph. Mismatches or bulges in the various off-target sites are shown with colored boxes or a dash in gray boxes, respectively. Off-target sites that lose the cognate TC motif within the editing window and thus might be expected to show lower off-target editing by eA3A, are noted with empty circles to the left. Asterisks indicate statistically significant differences in editing efficiencies observed between the indicated samples at each site (* p < 0.05, ** p < 0.005, *** p < 0.0005). All statistical testing was performed using two-tailed Student's t-test according to the method of Benjamini, Krieger, and Yekutieli without assuming equal variances between samples.