A cytosine deaminase for programmable single-base RNA editing
Author(s)Abudayyeh, Omar O.; Gootenberg, Jonathan S; Franklin, Brian; Koob, Jeremy; Kellner, Max J.; Ladha, Alim; Joung, Julia; Kirchgatterer, Paul; Cox, David B. T.; Zhang, Feng; ... Show more Show less
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Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive b-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs.
DepartmentMcGovern Institute for Brain Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
American Association for the Advancement of Science (AAAS)
Abudayyeh, Omar O. et al. "A cytosine deaminase for programmable single-base RNA editing." Science 365, 6451 (July 2019): 382-386 © 2019 American Association for the Advancement of Science
Author's final manuscript