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

Base editors enable targeted single-nucleotide conversion 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 and codon usage, and ancestral reco...

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Detalles Bibliográficos
Autores principales: Koblan, Luke W., Doman, Jordan L., Wilson, Christopher, Levy, Jonathan M., Tay, Tristan, Newby, Greg A., Maianti, Juan Pablo, Raguram, Aditya, Liu, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126947/
https://www.ncbi.nlm.nih.gov/pubmed/29813047
http://dx.doi.org/10.1038/nbt.4172
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author Koblan, Luke W.
Doman, Jordan L.
Wilson, Christopher
Levy, Jonathan M.
Tay, Tristan
Newby, Greg A.
Maianti, Juan Pablo
Raguram, Aditya
Liu, David R.
author_facet Koblan, Luke W.
Doman, Jordan L.
Wilson, Christopher
Levy, Jonathan M.
Tay, Tristan
Newby, Greg A.
Maianti, Juan Pablo
Raguram, Aditya
Liu, David R.
author_sort Koblan, Luke W.
collection PubMed
description Base editors enable targeted single-nucleotide conversion 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 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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spelling pubmed-61269472018-11-29 Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction Koblan, Luke W. Doman, Jordan L. Wilson, Christopher Levy, Jonathan M. Tay, Tristan Newby, Greg A. Maianti, Juan Pablo Raguram, Aditya Liu, David R. Nat Biotechnol Article Base editors enable targeted single-nucleotide conversion 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 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. 2018-05-29 2018-10 /pmc/articles/PMC6126947/ /pubmed/29813047 http://dx.doi.org/10.1038/nbt.4172 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Koblan, Luke W.
Doman, Jordan L.
Wilson, Christopher
Levy, Jonathan M.
Tay, Tristan
Newby, Greg A.
Maianti, Juan Pablo
Raguram, Aditya
Liu, David R.
Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title_full Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title_fullStr Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title_full_unstemmed Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title_short Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
title_sort improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126947/
https://www.ncbi.nlm.nih.gov/pubmed/29813047
http://dx.doi.org/10.1038/nbt.4172
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