The sequence of the protospacer is shown to the right of the mutation, with the PAM in blue and the target base in red with a subscripted number indicating its position within the protospacer. Underneath each sequence are the percentages of total sequencing reads with the corresponding base. Cells were treated as described in the Methods. a, The Alzheimer’s disease-associated APOE4 allele was converted to APOE3r in mouse astrocytes by BE3 in 74.9% of total reads. Two nearby Cs are also converted to Ts, but with no change to the predicted sequence of the resulting protein. Identical treatment of these cells with wild-type Cas9 and a 200-nt ssDNA donor results in 0.3% correction, with 26.1% indel formation. b, The cancer-associated p53 Y163C mutation is corrected by BE3 in 7.6% of nucleofected human breast cancer cells with 0.7% indel formation. Identical treatment of these cells with wild-type Cas9 and donor ssDNA results in no mutation correction with 6.1% indel formation.