Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction

Luke W. Koblan; Jordan L. Doman; Christopher Wilson; Jonathan M. Levy; Tristan Tay; Gregory A. Newby; Juan Pablo Maianti; Aditya Raguram; David R. Liu

doi:10.1038/nbt.4172

Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction

Luke W. Koblan, Jordan L. Doman, Christopher Wilson, Jonathan M. Levy, Tristan Tay, Gregory A. Newby, Juan Pablo Maianti, Aditya Raguram, David R. Liu

Research output: Contribution to journal › Article › peer-review

549 Scopus citations

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.

Original language	English (US)
Pages (from-to)	843-848
Number of pages	6
Journal	Nature biotechnology
Volume	36
Issue number	9
DOIs	https://doi.org/10.1038/nbt.4172
State	Published - Oct 1 2018
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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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.",

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.}",

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AU - Doman, Jordan L.

AU - Wilson, Christopher

AU - Levy, Jonathan M.

AU - Tay, Tristan

AU - Newby, Gregory A.

AU - Maianti, Juan Pablo

AU - Raguram, Aditya

AU - Liu, David R.

PY - 2018/10/1

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AB - 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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Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction

Abstract

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