Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo.
Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo.
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DOI：
10.1021/acs.analchem.0c03400
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发表时间：
2020-12
影响因子：
7.4
通讯作者：
Xueli Zhu;Bin Qu;Zhan‐Ming Ying;Jin-Wen Liu;Zhenkun Wu;R. Yu;Jian-hui Jiang
中科院分区：
文献类型：
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作者：
Xueli Zhu;Bin Qu;Zhan‐Ming Ying;Jin-Wen Liu;Zhenkun Wu;R. Yu;Jian-hui Jiang
DNA分子探针已成为RNA成像的有力工具。然而，细胞特异性递送的障碍和其他问题，如稳定性不足、灵敏度有限或反应动力学缓慢，阻碍了DNA分子探针在体内的进一步应用。在此，我们报告了一种适体拴系的DNA聚合物，用于通过DNA级联反应在体内进行RNA的细胞特异性运输和扩增成像。DNA聚合物通过使用两个功能性DNA单体的引发剂触发的杂交链反应来构建。所制备的DNA聚合物显示出低细胞毒性和良好的抗核酸酶降解的稳定性，并且能够通过适体-受体结合实现DNA回路的细胞特异性运输。此外，将发夹C1和C2的反应物组装在DNA聚合物上加速了响应动力学并提高了级联反应的灵敏度。我们还表明，DNA聚合物能够通过静脉注射在活细胞和体内对microRNA-21进行有效成像。DNA聚合物为体内靶向和扩增RNA成像提供了一个有价值的平台，这对早期临床诊断和治疗具有重要意义。
DNA molecular probes have emerged as a powerful tool for RNA imaging. Hurdles in cell-specific delivery and other issues such as insufficient stability, limited sensitivity, or slow reaction kinetics, however, hinder the further application of DNA molecular probes in vivo. Herein, we report an aptamer-tethered DNA polymer for cell-specific transportation and amplified imaging of RNA in vivo via a DNA cascade reaction. DNA polymers are constructed through an initiator-triggered hybridization chain reaction using two functional DNA monomers. The prepared DNA polymers show low cytotoxicity and good stability against nuclease degradation and enable cell-specific transportation of DNA circuits via aptamer-receptor binding. Moreover, assembling the reactants of hairpins C1 and C2 on the DNA polymers accelerates the response kinetics and improves the sensitivity of the cascade reaction. We also show that the DNA polymers enable efficient imaging of microRNA-21 in live cells and in vivo via intravenous injection. The DNA polymers provide a valuable platform for targeted and amplified RNA imaging in vivo, which holds great implications for early clinical diagnosis and therapy.