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. 2022 Apr 4;40(9):1378–1387. doi: 10.1038/s41587-022-01256-8

Fig. 6. Application of DddA11 variant to install pathogenic mutations at non-TC targets in HEK293T cells.

Fig. 6

a, Use of DdCBEs to install disease-associated target mutations in human mtDNA. (V, valine; I, isoleucine; A, alanine; T, threonine; Q, glutamine; ∗, stop). b–d, Mitochondrial base editing efficiencies of HEK293T cells treated with canonical or evolved ND4.3-DdCBE (b), ND4.2-DdCBE (c) and ND5.4-DdCBE (d). On-target cytosines are colored green, blue or red, respectively. Cells expressing the DddA11 variant of DdCBE were isolated by FACS for high-throughput sequencing. The split orientation, target spacing region and corresponding encoded amino acids are shown. Nucleotide sequences boxed in dotted lines are part of the TALE binding site. e, f, Oxygen consumption rate (OCR) (e) and relative values of respiratory parameters (f) in sorted HEK293T cells treated with the DddA11 variant of ND4.2-DdCBE or ND5.4-DdCBE. For b–f, values and error bars reflect the mean ± s.d. of n = 3 independent biological replicates, except that ND4.2-DdCBE in e and f reflects n = 2 independent biological replicates. *P < 0.05, **P < 0.01 and ***P < 0.001 by Student’s unpaired two-tailed t-test.