Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction.
Nat Biotechnol
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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. |
Year of Publication | 2018
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Journal | Nat Biotechnol
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Volume | 36
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Issue | 9
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Pages | 843-846
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Date Published | 2018 10
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ISSN | 1546-1696
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DOI | 10.1038/nbt.4172
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PubMed ID | 29813047
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PubMed Central ID | PMC6126947
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Grant list | RM1 HG009490 / HG / NHGRI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
R35 GM118062 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
T32 GM095450 / GM / NIGMS NIH HHS / United States
R01 EB022376 / EB / NIBIB NIH HHS / United States
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