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基于细胞内熵驱动的多位点 DNA 计算用于肿瘤进展判别。

Intracellular Entropy-Driven Multi-Bit DNA Computing for Tumor Progression Discrimination.

机构信息

Institute of Analytical Chemistry and Instrument for Life Science, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xianning West Road, Xi'an, Shaanxi, 710049, China.

Institute of Molecular Medicine, Renji Hospital, School of Medicine and School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.

出版信息

Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13267-13272. doi: 10.1002/anie.202001598. Epub 2020 May 27.

DOI:10.1002/anie.202001598
PMID:32367682
Abstract

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.

摘要

肿瘤的进展,如转移,是复杂的事件,涉及不同的 miRNAs 和酶的异常表达。通过计算 DNA 纳米技术在活细胞中监测这些生物分子,可能可以通过数字输出来区分肿瘤的进展。在此,我们报告了细胞内熵驱动的多价 DNA 电路,以实现多比特计算,用于同时分析细胞内端粒酶和 microRNAs,包括 miR-21 和 miR-31。这三种生物分子可以触发各自的 DNA 链置换循环反应以进行信号放大。通过荧光成像进行可视化,并将其信号输出编码为不同细胞类型的多比特二进制码。结果可以区分非致瘤性、恶性和转移性乳腺细胞以及各自的肿瘤。该 DNA 计算电路进一步在微流控芯片中进行,以区分稀有共培养的细胞,这为临床样本的分析提供了潜力。

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