期刊
CELL
卷 178, 期 1, 页码 122-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.05.049
关键词
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资金
- University of Chicago
- National Institute of General Medical Sciences [R35 GM119840]
- National Human Genome Research Institute of the National Institutes of Health [RM1 HG008935]
- Cancer Center Support Grant of the University of Chicago Medicine Comprehensive Cancer Center [P30 CA14599]
- University of Chicago Pritzker School of Medicine
- Chicago Fellows Program
Epitranscriptomic regulation controls information flow through the central dogma and provides unique opportunities for manipulating cells at the RNA level. However, both fundamental studies and potential translational applications are impeded by a lack of methods to target specific RNAs with effector proteins. Here, we present CRISPR-Cas-inspired RNA targeting system (CIRTS), a protein engineering strategy for constructing programmable RNA control elements. We show that CIRTS is a simple and generalizable approach to deliver a range of effector proteins, including nucleases, degradation machinery, translational activators, and base editors to target transcripts. We further demonstrate that CIRTS is not only smaller than naturally occurring CRISPR-Cas programmable RNA binding systems but can also be built entirely from human protein parts. CIRTS provides a platform to probe fundamental RNA regulatory processes, and the human-derived nature of CIRTS provides a potential strategy to avoid immune issues when applied to epitranscriptome-modulating therapies.
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