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

Nat Chem. 2020 Jan;12(1):26-35. doi: 10.1038/s41557-019-0369-8. Epub 2019 Nov 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Video-Audio Media

MeSH terms

  • Animals
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Benzimidazoles / chemistry
  • Chlorocebus aethiops
  • DNA / chemistry
  • DNA / pharmacology*
  • Dengue Virus / chemistry
  • Dengue Virus / drug effects*
  • Dengue Virus / isolation & purification*
  • Fluoresceins / chemistry
  • Fluorescent Dyes / chemistry
  • Hep G2 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Microscopy, Confocal / methods
  • Microscopy, Fluorescence / methods
  • Nanostructures / chemistry*
  • Protein Domains
  • Vero Cells
  • Viral Envelope Proteins / chemistry

Substances

  • Aptamers, Nucleotide
  • Benzimidazoles
  • Fluoresceins
  • Fluorescent Dyes
  • Viral Envelope Proteins
  • 6-carboxyfluorescein
  • DNA
  • bisbenzimide ethoxide trihydrochloride