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

Authors
Kwon, Paul S.
Ren, Shaokang
Kwon, Seok Joon
Kizer, Megan E.
Kuo, Lili
Xie, Mo
Zhu, Dan
Zhou, Feng
Zhang, Fuming
Kim, Domyoung
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2020-01-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
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.
Abstract
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.
Description
Nature Chemistry, 12, 26–35
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Nature
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Nature Chemistry
https://harc.rpi.edu/
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A full text version is available in DSpace@RPI
Open Access