Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition
| Autor: | Domyoung Kim, Keith Fraser, Shaokang Ren, Xing Wang, Nadrian C. Seeman, Fuming Zhang, Feng Zhou, Laura D. Kramer, Megan E. Kizer, Paul S. Kwon, Jonathan S. Dordick, Jie Chao, Seok Joon Kwon, Robert J. Linhardt, Lili Kuo, Mo Xie, Dan Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
General Chemical Engineering
Aptamer Protein domain Computational biology DNA nanostructures Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Epitope Article chemistry.chemical_compound Protein Domains Viral Envelope Proteins Chlorocebus aethiops Animals Humans Avidity Binding site Nucleic-acid therapeutics Vero Cells Fluorescent Dyes Microscopy Confocal 010405 organic chemistry General Chemistry DNA Hep G2 Cells Aptamers Nucleotide Dengue Virus Ligand (biochemistry) Fluoresceins 0104 chemical sciences Nanostructures Biosensors Nanomedicine chemistry Microscopy Fluorescence Benzimidazoles Biosensor |
| Zdroj: | Nature Chemistry |
| ISSN: | 1755-4349 1755-4330 |
| Popis: | 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. DNA is capable of self-assembling into a wide range of user-defined structures and so can be used as a scaffold to arrange binding motifs with nanometre precision. Now, DNA has been used to accurately display aptamers that fit the repeated epitope pattern of a dengue viral antigen to produce a nanostructure that can be a potent viral inhibitor or a fluorescent sensor. |
| Databáze: | OpenAIRE |
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