C12Y201/01032

G-TO-T BASE EDITORS AND USES THEREOF

The present disclosure provides for base editors which satisfy a need in the art for installation of targeted transversions of guanine (G) to thymine (T), or correspondingly, transversions of adenine (A) to cytosine (C). The domains of the disclosed base editors include a nucleic acid programmable DNA binding protein and a guanine oxidase or a guanine methyltransferase. The base editors may be engineered through the use of continuous or non-continuous evolution systems. In particular, the present disclosure provides for guanine-to-thymine (or cytosine-to-adenine) base editors that can install single-base trans version mutations. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising, and vectors and kits useful for the generation of, guanine-to-thymine base editors. Cells containing such vectors and cells containing base editors and guide RNAs are also provided. Further provided are methods of treatment comprising administering the base editors to a subject in need thereof.