Figure 2.

Possible DNA Base Editor Side Effects

(A) Schematic diagram of the mechanism behind CBE- and ABE-induced genome-wide off-target DNA mutations. The Cas9-sgRNA complex binds with mismatched DNA targets in the genome, allowing the linked deaminase to alter bases in the exposed ssDNA. (B) Unwanted on-target effects including the generation of bystander mutations within activity windows of base editors, inaccurate transversion mutation of target base via a CBE, and cytosine conversions mediated by the catalysis activity of an ABE. (C) Cytidine deaminases exhibit sgRNA-independent, genome-wide deamination effects. (D) Both cytidine and adenosine deaminases exhibit sgRNA-independent, transcriptome-wide deamination effects.