期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07322-7
关键词
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资金
- IRPs of NIDDK
- NHLBI
- Ministry of Health & Welfare, Republic of Korea [HI15C1184, HI17C2369]
- NSF graduate fellowship
- DARPA [HR0011-17-2-0049]
- U.S. NIH [RM1 HG009490, R01 EB022376, U01 AI142756, R35 GM118062]
- HHMI
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL005907] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [RM1HG009490] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI142756] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB022376] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK061000] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R35GM118062] Funding Source: NIH RePORTER
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 center dot T-to-G center dot C edits. Among CBEs, SaBE3 and BE4, result in the highest frequencies of anticipated C center dot G-to-T center dot 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.
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