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.
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All data supporting the findings of this work are available within this paper (figures, videos and description) and its Supplementary Information. All other data are available from the corresponding authors upon request.
The SEQUIN program used in this study is available from the corresponding authors upon reasonable request.
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We thank the core facilities at RPI-CBIS, Wadsworth Center of New York State Department of Health, Organic Electronics and Information Displays and Jiangsu Key Laboratory and Institute of Advanced Materials of Nanjing University of Posts and Telecommunications (China). This work was funded by an RPI-CBIS start-up fund and award, a gift fund from HT Materials Corporation to X.W., the Ministry of Science and Technology of China (2017YFA0205302), the National Science Foundation of China (21922408 and 61771253), the Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars (BK20190038) to J.C., the Global Research Laboratory Program through the National Research Foundation of Korea (2014K1A1A2043032) to J.S.D. and S.-J.K., and the National Institute of Health (DK111958) to R.J.L. The microscopy for time-lapsed analysis is supported by the National Science Foundation (NSF-MRI-1725984).
The authors declare no competing interests.
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Supplementary materials, methods, Figs. 1–9, Tables 1–11, notes and references.
Time-lapsed, live confocal imaging of dengue cell internalization.
Time-lapsed, live confocal imaging of DNA star-bound dengue losing cell internalization ability.
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Kwon, P.S., Ren, S., Kwon, S. et al. Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition. Nat. Chem. (2019) doi:10.1038/s41557-019-0369-8