FIGURE 2.

Base editing tools and therapeutic approaches. (A) Base editors consist of Cas nickases fused to cytosine (CBEs) or adenine ssDNA deaminases (ABEs). CBEs are fused to either AID or APOBEC1 (pink), which convert C into U, whereas ABEs are fused to an evolved TadA (TadA*) followed by a wild-type TadA fusion (brown), which convert A into I. The consequent G:U and T:I mismatches are then corrected by the cellular DNA repair mechanisms. To favor the correction of the non-edited nucleotides by the DNA mismatch repair machinery, the nickase introduces a “nick” in the unedited strand. The correction of the non-edited strand results in a final conversion of C:G into T:A base pairs and A:T into G:C base pairs by CBEs and ABEs, respectively. CBEs are usually fused to the UGI to prevent the rapid removal of uracil by BER (blue). (B) Base editing therapeutic approaches include the repair of pathogenic genes by correcting point mutations or the inactivation of toxic genes by generating a premature stop codon.