Journal
NATURE BIOTECHNOLOGY
Volume 36, Issue 9, Pages 843-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.4172
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Funding
- Ono Pharma Foundation
- DARPA [HR0011-17-2-0049]
- US NIH [RM1 HG009490, R35 GM118062, R01 EB022376]
- HHMI
- NCI [P30CCA14051]
- NIH [T32 GM095450]
- NSF
- Hertz Foundation
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Base editors enable targeted single-nucleotide conversions in genomic DNA. Here we show that expression levels are a bottleneck in base-editing efficiency. We optimize cytidine (BE4) and adenine (ABE7.10) base editors by modification of nuclear localization signals (NLS) and codon usage, and ancestral reconstruction of the deaminase component. The resulting BE4max, AncBE4max, and ABEmax editors correct pathogenic SNPs with substantially increased efficiency in a variety of mammalian cell types.
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