Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition

• DOI: 10.1038/s41557-019-0369-8
• Publication Date: 2019-11-25T17:02:50Z
• Authors: Paul S. Kwon; Shaokang Ren; Seok-Joon Kwon; Megan E. Kizer; Lili Kuo; Mo Xie; Dan Zhu; Feng Zhou; Fuming Zhang; Domyoung Kim; Keith Fraser; Laura D. Kramer; Nadrian C. Seeman; Jonathan S. Dordick; Robert J. Linhardt; Jie Chao; Xing Wang
• Keywords: Aptamer; DNA origami; Avidity; Molecular Recognition; DNA nanotechnology; Molecular machine

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.