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Optimized base editors enable efficient editing in cells, organoids and mice

CRISPR base editing enables the creation of targeted single-base conversions without generating double-stranded breaks. However, the efficiency of current base editors is very low in many cell types. We reengineered the sequences of BE3, BE4Gam, and xBE3 by codon optimization and incorporation of ad...

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Main Authors: Zafra, Maria Paz (Author) , Schatoff, Emma M. (Author) , Katti, Alyna (Author) , Foronda, Miguel (Author) , Breinig, Marco (Author) , Schweitzer, Anabel (Author) , Simon, Amber (Author) , Han, Teng (Author) , Goswami, Sukanya (Author) , Montgomery, Emma (Author) , Thibado, Jordana (Author) , Kastenhuber, Edward R. (Author) , Sánchez-Rivera, Francisco J. (Author) , Shi, Junwei (Author) , Vakoc, Christopher R. (Author) , Lowe, Scott W. (Author) , Tschaharganeh, Darjus-Felix (Author) , Dow, Lukas E. (Author)
Format: Article (Journal)
Language:English
Published: 3 July 2018
In: Nature biotechnology
Year: 2018, Volume: 36, Issue: 9, Pages: 888-893
ISSN:1546-1696
DOI:10.1038/nbt.4194
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/nbt.4194
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Author Notes:Maria Paz Zafra, Emma M. Schatoff, Alyna Katti, Miguel Foronda, Marco Breinig, Anabel Y. Schweitzer, Amber Simon, Teng Han, Sukanya Goswami, Emma Montgomery, Jordana Thibado, Edward R. Kastenhuber, Francisco J. Sánchez-Rivera, Junwei Shi, Christopher R. Vakoc, Scott W. Lowe, Darjus F. Tschaharganeh & Lukas E. Dow
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Summary:CRISPR base editing enables the creation of targeted single-base conversions without generating double-stranded breaks. However, the efficiency of current base editors is very low in many cell types. We reengineered the sequences of BE3, BE4Gam, and xBE3 by codon optimization and incorporation of additional nuclear-localization sequences. Our collection of optimized constitutive and inducible base-editing vector systems dramatically improves the efficiency by which single-nucleotide variants can be created. The reengineered base editors enable target modification in a wide range of mouse and human cell lines, and intestinal organoids. We also show that the optimized base editors mediate efficient in vivo somatic editing in the liver in adult mice.
Item Description:Gesehen am 11.03.2020
Physical Description:Online Resource
ISSN:1546-1696
DOI:10.1038/nbt.4194

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