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

Zafra, M. P., Schatoff, E. M., Katti, A., Foronda, M., Breinig, M., Schweitzer, A. Y., Simon, A., Han, T., Goswami, S., Montgomery, E., Thibado, J., Kastenhuber, E. R., Sanchez-Rivera, F. J., Shi, J., Vakoc, C. R., Lowe, S. W., Tschaharganeh, D. F., Dow, L. E. (October 2018) Optimized base editors enable efficient editing in cells, organoids and mice. Nat Biotechnol, 36 (9). pp. 888-896. ISSN 1087-0156

URL: https://www.ncbi.nlm.nih.gov/pubmed/29969439
DOI: 10.1038/nbt.4194

Abstract

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 Type: Paper
Subjects: Investigative techniques and equipment > CRISPR-Cas9
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matthew Dunn
Date: 1 October 2018
Date Deposited: 21 Sep 2018 19:00
Last Modified: 21 Sep 2018 19:00
PMCID: PMC6130889
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37210

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