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Targeting fidelity of adenine and cytosine base editors in mouse embryos.

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.

SUBMITTER: Lee HK

PROVIDER: S-EPMC6238002 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Targeting fidelity of adenine and cytosine base editors in mouse embryos.

Lee Hye Kyung HK Willi Michaela M Miller Shannon M SM Kim Sojung S Liu Chengyu C Liu David R DR Hennighausen Lothar L

Nature communications 20181115 1

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 ...[more]

PMID: 30442934

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