The authors developed a new genome-editing method called base editing, which allows for the direct and irreversible conversion of one DNA base to another without requiring double-stranded DNA (dsDNA) cleavage or a donor template. They engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme, which can be programmed with a guide RNA to convert cytosine (C) to uracil (U) without inducing dsDNA breaks. This results in a C→T (or G→A) substitution. The "base editors" can convert C within a window of approximately five nucleotides and efficiently correct various point mutations relevant to human disease. In human and mouse cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor (UGI) and use a Cas9 nickase targeting the non-edited strand manipulate the cellular DNA repair response to favor desired base-editing outcomes, leading to permanent correction of ~15-75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing for point mutations.The authors developed a new genome-editing method called base editing, which allows for the direct and irreversible conversion of one DNA base to another without requiring double-stranded DNA (dsDNA) cleavage or a donor template. They engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme, which can be programmed with a guide RNA to convert cytosine (C) to uracil (U) without inducing dsDNA breaks. This results in a C→T (or G→A) substitution. The "base editors" can convert C within a window of approximately five nucleotides and efficiently correct various point mutations relevant to human disease. In human and mouse cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor (UGI) and use a Cas9 nickase targeting the non-edited strand manipulate the cellular DNA repair response to favor desired base-editing outcomes, leading to permanent correction of ~15-75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing for point mutations.