@misc{10481/109751, year = {2018}, month = {7}, url = {https://hdl.handle.net/10481/109751}, 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.}, organization = {NIH/NCI (CA195787-01), (U54OD020355), (1 F31 CA224800-01.), (F31CA192835), (CA 181280-01)}, organization = {Starr Cancer Consortium (I10-0095)}, organization = {American Cancer Society (RSG-17-202-01)}, organization = {Stand Up to Cancer (SU2C-AACR-DT22-17)}, organization = {American Association for Cancer Research SU2C}, organization = {National Cancer Institute (NCI) NIH T32 CA203702}, organization = {NIH T32GM07739}, organization = {HHMI Hanna Gray Fellow (5T32CA160001)}, organization = {Geoffrey Beene Chair of Cancer Biology/Howard Hughes Medical Institute}, organization = {Helmholtz Association (VH-NG-1114)}, organization = {German Research Foundation (DFG) B05, SFB/TR 209}, publisher = {Springer Nature}, keywords = {CRISPR-Cas9}, keywords = {Base Editing}, keywords = {Organoids}, keywords = {Cancer-associated mutations}, keywords = {Mouse models}, title = {Optimized base editors enable efficient editing in cells, organoids and mice}, doi = {10.1038/nbt.4194}, author = {Zafra, María Paz and Schatoff, Emma M. and Katti, Alyna and Foronda, Miguel and Breinig, Marco and Schweitzer, Anabel Y. and Simon, Amber and Han, Teng and Goswami, Sukanya and Montgomery, Emma and Thibado, Jordana and Kastenhuber, Edward R. and Sánchez-Rivera, Francisco J. and Shi, Junwei and Vakoc, Christopher R. and Lowe, Scott W. and Tschaharganeh, Darjus F. and Dow, Lukas E.}, }