期刊
CELL
卷 180, 期 5, 页码 1018-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.02.011
关键词
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资金
- NIH Director's New Innovator Award [1DP2GM126892]
- Gates Foundation [OPP1160667]
- Arizona Biomedical Research Commission New Investigator Award [ADHS16-162400]
- Alfred P. Sloan Fellowship [FG-2017-9108]
- Gordon and Betty Moore Foundation [6984]
- NIH [1R21AI136571]
- DARPA Young Faculty Award [D17AP00026]
- Arizona State University
- Bill and Melinda Gates Foundation [OPP1160667] Funding Source: Bill and Melinda Gates Foundation
The ability to identify single-nucleotide mutations is critical for probing cell biology and for precise detection of disease. However, the small differences in hybridization energy provided by single-base changes makes identification of these mutations challenging in living cells and complex reaction environments. Here, we report a class of de novodesigned prokaryotic riboregulators that provide ultraspecific RNA detection capabilities in vivo and in cell-free transcription-translation reactions. These single-nucleotide-specific programmable riboregulators (SNIPRs) provide over 100-fold differences in gene expression in response to target RNAs differing by a single nucleotide in E. coli and resolve single epitranscriptomic marks in vitro. By exploiting the programmable SNIPR design, we implement an automated design algorithm to develop riboregulators for a range of mutations associated with cancer, drug resistance, and genetic disorders. Integrating SNIPRs with portable paper-based cell-free reactions enables convenient isothermal detection of cancer-associated mutations from clinical samples and identification of Zika strains through unambiguous colorimetric reactions.
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