Fig. 1: Generation of DddA11 for inducing m.G11185A base editing on MT-ND4 gene, and its limitations for manufacturing MT-ND4 mutant mice.
From: In vivo mitochondrial base editing restores genotype and visual function in a mouse model of LHON
a Schematic illustration of DddA11 in mouse MT-ND4 gene. Base editing window is annotated with black, and the TALE binding sequence with gray. Desired editing locus was shown in red (m.G11185A). b Editing efficiency of m.G11185A in buffer injected blastocysts (n = 5), DddA11 injected blastocysts (n = 20), and DddA11 injected pups (n = 35). The exact p-values were 1.33861E-14 in buffer injected blastocysts and DddA11 injected blastocysts, 0.419 in buffer injected blastocysts and DddA11 injected pups. (ns not significant, ***p < 0.001 using Student’s two-tailed t-test). c MT-ND4 gene mutation alleles induced by DddA11 in blastocysts. Yellow bars indicate the frequencies of m.G11185A without undesired editing. Targeted editing loci were shown in red (m.G11185A), and undesired editing loci were in blue. d Mitochondrial genome-wide off-target editing in buffer injected blastocysts and DddA11 injected blastocysts. On-target editing efficiencies were shown in blue (m.G11185A), and off-targets were in black.
