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bioRxiv · 10.1101/608380

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

Kwon, P. S.·Ren, S.·Kwon, S.-J.·Kizer, M. E.·Kuo, L.·Zhou, F.·Zhang, F.·Kim, D.·Fraser, K.·Kramer, L. D.·Seeman, N. C.·Dordick, J. S.·Linhardt, R. J.·Chao, J.·Wang, X.
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Abstract

DNA, when folded into nanostructures of customizable shapes, is capable of spacing and arranging external ligands in a desired geometric pattern with nanometer-precision. This allows DNA to serve as an excellent, biocompatible scaffold for complex spatial pattern-recognizing displays. In this report, we demonstrate that a templated designer DNA nanostructure achieves multi-ligand display with precise spatial pattern-recognition, representing a unique strategy in synthesizing potent viral sensors and inhibitors. Specifically, a star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue virus envelope protein domain-III (ED3)-binding aptamers into a 2D pattern precisely matching the pentagonal arrangement of ED3 clusters on the dengue viral surface. The resulting spatial pattern recognition and multivalent interactions achieve high dengue-binding avidity, conferring direct, highly-sensitive, facile, low-cost, and rapid sensing as well as potent viral inhibition capability. Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens, including bacteria and microbial-toxins, by generating the requisite ligand patterns on customized DNA nanoarchitectures.

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Kwon, P. S., Ren, S., Kwon, S.-J., Kizer, M. E., Kuo, L., Zhou, F., Zhang, F., Kim, D., Fraser, K., Kramer, L. D., Seeman, N. C., Dordick, J. S., Linhardt, R. J., Chao, J., Wang, X.. 2019-04-13. Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition. https://doi.org/10.1101/608380

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