T:A to A:T base editing through adenosine methylation

Application No.
PCT/US2020/021398
Broad Case No.
BI-10513
Inventors

David Liu, Jessie Davis, Jordan Leigh Doman, Kevin Zhao, Michelle Richter

Abstract

The present disclosure provides for base editors which satisfy a need in the art for installation of targeted transversions of thymine (T) to adenine (A), or correspondingly, trans versions of adenine (A) to thymine (T). The nucleobase editor domains include a nucleic acid programmable DNA binding protein and an adenosine methyltransferase domain. The base editors may be engineered through the use of continuous or non-continuous evolution systems, such as phage-assisted continuous evolution (PACE). In particular, the present disclosure provides for evolved adenine-to-thymine (or thymine-to-adenine) base editor variants that overcome deficiencies in the art for base editors that can install single-base A:T to T:A transversion mutations. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, pharmaceutical compositions comprising, and vectors and kits for the generation of, targeted base editors are provided. In some embodiments, cells containing such vectors are provided. In some embodiments, methods of treatment comprising administering the base editors are provided.

Date Published
Date Issued
Published Patent Application
WO 2020/181193
File upload PDF