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

• Published in: Nature chemistry Vol. 12; no. 1; pp. 26 - 35
• Main Authors: Kwon, Paul S., Ren, Shaokang, Kwon, Seok-Joon, Kizer, Megan E., Kuo, Lili, Xie, Mo, Zhu, Dan, Zhou, Feng, Zhang, Fuming, Kim, Domyoung, Fraser, Keith, Kramer, Laura D., Seeman, Nadrian C., Dordick, Jonathan S., Linhardt, Robert J., Chao, Jie, Wang, Xing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2020; Nature Publishing Group
• Subjects: 631/61/51/391; 639/925/350/59; 639/925/352; 639/925/926/1049; Analytical Chemistry; Animals; Antigens; Aptamers; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - pharmacology; Architecture; Avidity; Benzimidazoles - chemistry; Binding sites; Biochemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chlorocebus aethiops; Dengue fever; Dengue Virus - chemistry; Dengue Virus - drug effects; Dengue Virus - isolation & purification; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - pharmacology; Epitopes; Fluoresceins - chemistry; Fluorescence; Fluorescent Dyes - chemistry; Hep G2 Cells; Humans; Inhibitors; Inorganic Chemistry; Microbial Sensitivity Tests; Microscopy, Confocal - methods; Microscopy, Fluorescence - methods; Nanostructure; Nanostructures - chemistry; Organic Chemistry; Pattern recognition; Physical Chemistry; Protein Domains; Self-assembly; Vector-borne diseases; Vero Cells; Viral diseases; Viral envelope proteins; Viral Envelope Proteins - chemistry
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-019-0369-8

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.