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

Kwon, Paul S.
Ren, Shaokang
Kwon, Seok Joon
Kizer, Megan E.
Kuo, Lili
Xie, Mo
Zhu, Dan
Zhou, Feng
Zhang, Fuming
Kim, Domyoung
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, P. S. Kwon, S. Ren1, S.-J. Kwon, M. E. Kizer, L. Kuo, M. Xie, D. Zhu, F. Zhou, F. Zhang, D. Kim, K. Fraser, L. D. Kramer, N. C. Seeman, J. S. Dordick, R. J. Linhardt, J. Chao, X. Wang, Nature Chemistry, 12, 26–35, 2020.
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.
Nature Chemistry, 12, 26–35
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Nature Chemistry
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