Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
This paper introduced cytosine base editing (CBE), a strategy that fuses a catalytically impaired Cas9 to a cytidine deaminase to directly convert C-G base pairs to T-A in genomic DNA without inducing double-strand breaks or requiring a donor template. The authors showed that within a programmable target window the deaminase converts cytosine to uracil, which is then read as thymine, and that inhibiting base-excision repair markedly improves editing efficiency. The approach achieved precise single-base correction in human and other mammalian cells.