Optimized base editors enable efficient editing in cells, organoids and mice Journal Article
| Authors: | 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.; Sánchez-Rivera, F. J.; Shi, J.; Vakoc, C. R.; Lowe, S. W.; Tschaharganeh, D. F.; Dow, L. E. |
| Article Title: | Optimized base editors enable efficient editing in cells, organoids and mice |
| 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. © 2018, Nature Publishing Group. All rights reserved. |
| Keywords: | adult; controlled study; single nucleotide polymorphism; nonhuman; letter; animal cell; mouse; cell line; animal experiment; in vivo study; liver; cell culture; mammals; efficiency; editor; nuclear localization sequences; adult mice; male; female; organoid; codon optimization; base conversion; human cell lines; single nucleotides; target modification; vector systems |
| Journal Title: | Nature Biotechnology |
| Volume: | 36 |
| Issue: | 9 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-09-01 |
| Start Page: | 888 |
| End Page: | 893 |
| Language: | English |
| DOI: | 10.1038/nbt.4194 |
| PROVIDER: | scopus |
| PMCID: | PMC6130889 |
| PUBMED: | 29969439 |
| DOI/URL: | |
| Notes: | Letter -- Export Date: 1 October 2018 -- Source: Scopus |
