Figure 8.

(a) Transition efficiencies for CBEs and ABE8e tested in this study in medaka across the entire protospacer are shown as mean with 95% confidence interval (CI). Each data point represents the mean efficiency for the locus (sgRNA) tested. N = represents the number of loci tested with the respective editor. n = total number of genomes used for quantification of editing efficiencies (a pool of five embryos was counted as five genomes). (a’) Simplified scheme only showing mean and CI. (b) Summary of dinucleotide preference for the tested base editors, calculated for the standard editing window (4-8). Each data point represents the mean editing efficiency of the corresponding editor for a particular protospacer position. (b’) Simplified scheme of overlaid dinucleotide logic. (c) Analysis of human pathogenic CDS SNVs annotated in ClinVar reveals that a remarkable portion of these SNVs have orthologous sequences in medaka or zebrafish that can be mimicked by CBEs or ABEs following editing window (4-8) and NGG PAM restrictions. Modeling SNVs mutations may be achieved with stringent criteria (no bystander mutations accepted, n = 1951) or less stringent selection (allowing bystander mutations ‘all’, n = 5896). Note: the number of SNVs shown for medaka + zebrafish, corresponds to a set-up in which these species are complementing each other.