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Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition.
Nature Chemistry ( IF 19.2 ) Pub Date : 2019-11-25 , DOI: 10.1038/s41557-019-0369-8
Paul S Kwon 1, 2, 3 , Shaokang Ren 1 , Seok-Joon Kwon 4 , Megan E Kizer 2 , Lili Kuo 5 , Mo Xie 1 , Dan Zhu 1 , Feng Zhou 6, 7 , Fuming Zhang 4 , Domyoung Kim 4 , Keith Fraser 4 , Laura D Kramer 5 , Nadrian C Seeman 6 , Jonathan S Dordick 4 , Robert J Linhardt 2, 4 , Jie Chao 1 , Xing Wang 2, 8
Affiliation  

DNA, when folded into nanostructures with a specific shape, is capable of spacing and arranging binding sites into a complex geometric pattern with nanometre precision. Here we demonstrate a designer DNA nanostructure that can act as a template to display multiple binding motifs with precise spatial pattern-recognition properties, and that this approach can confer exceptional sensing and potent viral inhibitory capabilities. A star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue envelope protein domain III (ED3)-targeting aptamers into a two-dimensional pattern precisely matching the spatial arrangement of ED3 clusters on the dengue (DENV) viral surface. The resulting multivalent interactions provide high DENV-binding avidity. We show that this structure is a potent viral inhibitor and that it can act as a sensor by including a fluorescent output to report binding. Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens by generating the requisite ligand patterns on customized DNA nanoarchitectures.

中文翻译:

设计师 DNA 架构为病毒传感和抑制提供了精确和多价的空间模式识别。

DNA,当折叠成具有特定形状的纳米结构时,能够以纳米精度将结合位点间隔和排列成复杂的几何图案。在这里,我们展示了一种设计 DNA 纳米结构,它可以作为模板显示具有精确空间模式识别特性的多个结合基序,并且这种方法可以赋予卓越的传感和有效的病毒抑制能力。构建了带有五个分子信标样基序的星形 DNA 结构,以将十个登革热包膜蛋白结构域 III (ED3) 靶向适体显示为与登革热 (DENV) 上 ED3 簇的空间排列精确匹配的二维模式) 病毒表面。由此产生的多价相互作用提供了高 DENV 结合亲和力。我们表明,这种结构是一种有效的病毒抑制剂,它可以通过包含荧光输出来报告绑定,从而充当传感器。我们的分子平台设计策略可以通过在定制的 DNA 纳米结构上生成必要的配体模式来适应检测和对抗其他致病病原体。
更新日期:2019-11-26
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