@article{7c851fcfa94a430081d19fe6b047263b,
title = "Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction",
abstract = "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.",
author = "Koblan, {Luke W.} and Doman, {Jordan L.} and Christopher Wilson and Levy, {Jonathan M.} and Tristan Tay and Newby, {Gregory A.} and Maianti, {Juan Pablo} and Aditya Raguram and Liu, {David R.}",
note = "Funding Information: Flow cytometry was supported by NCI P30CCA14051. L.W.K. is an NSF Graduate Research Fellow and was supported by NIH Training Grant T32 GM095450. J.L.D. gratefully acknowledges graduate fellowship support from the NSF and Hertz Foundation. We thank J. Coller, G. Hansen, M. Weiss, and A. Sharma for helpful discussions. Funding Information: This work was supported by the Ono Pharma Foundation, DARPA HR0011-17-2-0049, US NIH RM1 HG009490, R01 EB022376, and R35 GM118062, and HHMI. Publisher Copyright: {\textcopyright} 2018, Nature Publishing Group. All rights reserved.",
year = "2018",
month = oct,
day = "1",
doi = "10.1038/nbt.4172",
language = "English (US)",
volume = "36",
pages = "843--848",
journal = "Nature biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "9",
}