Improving Cytidine and Adenine Base Editors by Expression Optimization and Ancestral Reconstruction

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2018 May 30

PMID 29813047

Citations 468

Authors

Luke W Koblan

Jordan L Doman

Christopher Wilson

Jonathan M Levy

Tristan Tay

Gregory A Newby

Juan Pablo Maianti

Aditya Raguram

David R Liu

Affiliations

Soon will be listed here.

Abstract

Base editors enable targeted single-nucleotide conversions in genomic DNA. Here we show that expression levels are a bottleneck in base-editing efficiency. We optimize cytidine (BE4) and adenine (ABE7.10) base editors by modification of nuclear localization signals (NLS) and codon usage, and ancestral reconstruction of the deaminase component. The resulting BE4max, AncBE4max, and ABEmax editors correct pathogenic SNPs with substantially increased efficiency in a variety of mammalian cell types.

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