Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 32, Pages 13267-13272Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202001598
Keywords
DNA nanotechnology; enzyme and RNA; microfluidic chip; molecular computing; tumor discrimination
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Funding
- National Natural Science Foundation of China [31671013, 21705124, 21874105]
- China Postdoctoral Science Foundation [2017M613102, 2018T111032, 2019M663658]
- Natural Science Foundation of Shaanxi Province [2018JC-001]
- Fundamental Research Funds for the Central Universities
- Young Talent Support Plan of Xian Jiaotong University
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Tumor progressions such as metastasis are complicated events that involve abnormal expression of different miRNAs and enzymes. Monitoring these biomolecules in live cells with computational DNA nanotechnology may enable discrimination of tumor progression via digital outputs. Herein, we report intracellular entropy-driven multivalent DNA circuits to implement multi-bit computing for simultaneous analysis of intracellular telomerase and microRNAs including miR-21 and miR-31. These three biomolecules can trigger respective DNA strand displacement recycling reactions for signal amplification. They are visualized by fluorescence imaging, and their signal outputs are encoded as multi-bit binary codes for different cell types. The results can discriminate non-tumorigenic, malignant and metastatic breast cells as well as respective tumors. This DNA computing circuit is further performed in a microfluidic chip to differentiate rare co-cultured cells, which holds a potential for the analysis of clinical samples.
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