Targeting fidelity of adenine and cytosine base editors in mouse embryos

Hye Kyung Lee (), Michaela Willi, Shannon M. Miller, Sojung Kim, Chengyu Liu, David R. Liu and Lothar Hennighausen ()
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Hye Kyung Lee: US National Institutes of Health
Michaela Willi: US National Institutes of Health
Shannon M. Miller: Broad Institute of MIT and Harvard
Sojung Kim: US National Institutes of Health
Chengyu Liu: Transgenic Core, National Heart, Lung, and Blood Institute, US National Institutes of Health
David R. Liu: Broad Institute of MIT and Harvard
Lothar Hennighausen: US National Institutes of Health

Nature Communications, 2018, vol. 9, issue 1, 1-6

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07322-7

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