Spatially Constrained DNA Nanomachines To Accelerate Kinetics in Response to External Input: Design and Bioanalysis
Spatially Constrained DNA Nanomachines To Accelerate Kinetics in Response to External Input: Design and Bioanalysis
复制标题
空间受限的 DNA 纳米机器加速响应外部输入的动力学：设计和生物分析
DOI：
10.1021/acs.analchem.0c00802
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发表时间：
2020
影响因子：
7.4
通讯作者：
Cheng Nansheng
中科院分区：
文献类型：
--
作者：
Zhou Rongxing;Hu Changjia;Jin Yanwen;Zhang Jie;Du Huan;Yang Peng;Chen Junbo;Hou Xi;eng;Cheng Nansheng
细胞利用空间组织来加速拥挤的细胞内环境中不同组分的反应动力学。受此启发，我们在此设计了一个空间约束的原则，以克服在DNA酶驱动的DNA纳米机器的响应动力学的限制。首先，我们提出了1型空间约束DNA纳米机器（scDN-1）通过共定位的适配体探针和动力单元（DNAzyme），允许DNA纳米机器完成更快的循环切割DNAzyme作为分子内反应。为了将scDN扩展到临床实践中，然后通过Holliday连接组装构建具有约束抗体探针的2型空间约束DNA纳米机器（scDN-2），其增加了有效局部浓度以获得改善的动力学。利用加速响应动力学，这种设计原理允许DNA纳米机器在30分钟内完成对真实的患者样本中的肿瘤标志物的响应，显著拓宽了DNA纳米机器在临床实践中的生物分析应用。
Cells take advantage of the spatial organization to accelerate the reaction kinetics of diverse components within a crowded intracellular environment. Inspired by this, we hereby designed a principle of spatial constraint to overcome limitations of response kinetics in DNAzyme-powered DNA nanomachines. First, we proposed the type-1 of spatially constrained DNA nanomachines (scDN-1) by co-localizing the aptamer probe and power unit (DNAzyme), allowing the DNA nanomachines to accomplish faster cyclic cleavage of DNAzyme as intramolecular reactions. To expand the scDN into the clinical practice, Type 2 spatially constrained DNA nanomachines (scDN-2) with constrained antibody probes were then constructed through Holliday junction assembly, which increased the effective local concentration to obtain the improved kinetics. With an accelerated response kinetics, this design principle allows DNA nanomachines to accomplish the response to tumor markers in real patients’ samples within 30 min, significantly broadening the bioanalytical applications of DNA nanomachines to clinical practice.