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Targeting fidelity of adenine and cytosine base editors in mouse embryos.
- Source :
-
Nature communications [Nat Commun] 2018 Nov 15; Vol. 9 (1), pp. 4804. Date of Electronic Publication: 2018 Nov 15. - Publication Year :
- 2018
-
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.
- Subjects :
- Alleles
Animals
Animals, Genetically Modified
CRISPR-Associated Protein 9 genetics
CRISPR-Associated Protein 9 metabolism
Embryo, Mammalian
Genetic Loci
Mice
Microinjections
Reproducibility of Results
Sensitivity and Specificity
Zygote
RNA, Guide, CRISPR-Cas Systems
Adenine metabolism
CRISPR-Cas Systems
Cytosine metabolism
Gene Editing methods
Point Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 30442934
- Full Text :
- https://doi.org/10.1038/s41467-018-07322-7