Journal Article

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

Zhu, Dan, Zhang, Fuming, Wang, Xing, Linhardt, Robert J, Kramer, Laura D, Kizer, Megan E, Seeman, Nadrian C, Dordick, Jonathan S, Zhou, Feng, Kwon, Seok-Joon, Kuo, Lili, Kim, Domyoung, Chao, Jie, Kwon, Paul S, Fraser, Keith, Xie, Mo, Ren, Shaokang

2020

Overview

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.

• Publisher: Nature Publishing Group,Nature Publishing Group UK
• Subject: Animals / Antigens / Aptamers / Aptamers, Nucleotide - chemistry / Aptamers, Nucleotide - pharmacology / Architecture / Avidity / Benzimidazoles - chemistry / Binding sites / 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 / Microbial Sensitivity Tests / Microscopy, Confocal - methods / Microscopy, Fluorescence - methods / Nanostructure / Nanostructures - chemistry / Pattern recognition / Protein Domains / Self-assembly / Vero Cells / Viral diseases / Viral envelope proteins / Viral Envelope Proteins - chemistry