Targeting Fidelity of Adenine and Cytosine Base Editors in Mouse Embryos

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Nov 17

PMID 30442934

Citations 46

Authors

Hye Kyung Lee

Michaela Willi

Shannon M Miller

Sojung Kim

Chengyu Liu

David R Liu

Lothar Hennighausen

Affiliations

Soon will be listed here.

Abstract

Base editing directly converts a target base pair into a different base pair in the genome of living cells without introducing double-stranded DNA breaks. While cytosine base editors (CBE) and adenine base editors (ABE) are used to install and correct point mutations in a wide range of organisms, the extent and distribution of off-target edits in mammalian embryos have not been studied in detail. We analyze on-target and proximal off-target editing at 13 loci by a variety of CBEs and ABE in more than 430 alleles generated from mouse zygotic injections using newly generated and published sequencing data. ABE predominantly generates anticipated A•T-to-G•C edits. Among CBEs, SaBE3 and BE4, result in the highest frequencies of anticipated C•G-to-T•A products relative to editing byproducts. Together, these findings highlight the remarkable fidelity of ABE in mouse embryos and identify preferred CBE variants when fidelity in vivo is critical.

Citing Articles

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