Title | Optimized base editors enable efficient editing in cells, organoids and mice. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Zafra MPaz, Schatoff EM, Katti A, Foronda M, Breinig M, Schweitzer AY, Simon A, Han T, Goswami S, Montgomery E, Thibado J, Kastenhuber ER, Sánchez-Rivera FJ, Shi J, Vakoc CR, Lowe SW, Tschaharganeh DF, Dow LE |
Journal | Nat Biotechnol |
Volume | 36 |
Issue | 9 |
Pagination | 888-893 |
Date Published | 2018 10 |
ISSN | 1546-1696 |
Keywords | Animals, Cell Line, CRISPR-Cas Systems, Gene Editing, Genetic Variation, Humans, 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. |
DOI | 10.1038/nbt.4194 |
Alternate Journal | Nat. Biotechnol. |
PubMed ID | 29969439 |
PubMed Central ID | PMC6130889 |
Grant List | T32 CA160001 / CA / NCI NIH HHS / United States U54 OD020355 / OD / NIH HHS / United States T32 CA203702 / CA / NCI NIH HHS / United States K22 CA181280 / CA / NCI NIH HHS / United States F31 CA192835 / CA / NCI NIH HHS / United States F31 CA224800 / CA / NCI NIH HHS / United States / / Howard Hughes Medical Institute / United States T32 GM007739 / GM / NIGMS NIH HHS / United States R01 CA195787 / CA / NCI NIH HHS / United States |
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