A cytosine deaminase for programmable single-base RNA editing

Author:

Abudayyeh Omar O.12ORCID,Gootenberg Jonathan S.12ORCID,Franklin Brian1ORCID,Koob Jeremy1ORCID,Kellner Max J.1ORCID,Ladha Alim13ORCID,Joung Julia13ORCID,Kirchgatterer Paul1ORCID,Cox David B. T.1,Zhang Feng1234ORCID

Affiliation:

1. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

2. McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

4. Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Adding to the RNA editing toolbox A previously developed RNA editing system called REPAIR can base edit A to I in RNA by fusing the adenine deaminase domain of ADAR2 with catalytically dead CRISPR-Cas13. Using directed evolution, Abudayyeh et al. demonstrated that the ADAR2 deaminase domain can be relaxed to accept other bases. This resulted in cytidine deamination activity, expanding the RNA editing toolbox for C-to-U conversion. This system, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), can edit on endogenous transcripts and enable modulation of posttranslational protein modification such as phosphorylation. Science , this issue p. 382

Funder

National Institutes of Health

National Institute of General Medical Sciences

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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