Structurally designed 'DNA star' creates ultrasensitive test for dengue virus

By folding snippets of DNA into the shape of a five-pointed star using structural DNA nanotechnology, researchers have created a trap that captures dengue virus as it floats in the bloodstream. Once sprung, the trap – which is nontoxic and is naturally cleared from the body – lights up. It’s the most sensitive test yet for the mosquito-borne diseases.

Published in the journal Nature Chemistry, this detection technique could be expanded to other viruses and adapted to kill the viruses it snares.

“This is more sensitive than any other way of detecting dengue, beating the clinical test by more than 100 fold,” said Xing Wang (ONC-PM), a University of Illinois chemistry professor and the corresponding author of the study. “The binding is tight and the specificity is high, enabling us to distinguish the presence of dengue on the first day of infection.”

Wang was a professor at the Rensselaer Polytechnic Institute at the time of the research, along with co-authors and Rensselaer professors Robert Linhardt and Jonathan Dordick.

A trap could be effective against many different viruses because, in order to infect their host, all viruses must first latch onto a cell wall and disgorge their genetic instructions into the cell. Structural DNA nanotechnology – an established method of folding strands of DNA into designed, customized geometric shapes and objects – offered the research team a nontoxic, biodegradable platform on which to construct a new trap, Wang said.

The spherical surface of dengue, like the closely related Zika virus, is studded with multiple latch points to catch a cell surface. By superimposing various DNA nanostructural shapes onto images of the virus, the team settled on a five-pointed star – they call it a “DNA star” – as the best match between points on the DNA shape and latch points on the virus.

Wang attached specific aptamers – molecules the viral latches will bind to – precisely to the tips and vertices of the star so they would align with the distribution of the latches on the virus.

“You could overlay the star onto the virus and target a whole hemisphere of the sphere precisely,” Wang said. “All the ligands that would target the antigens of this virus would overlay perfectly with a DNA star. If we were only able to make a connection in one place it would be a weak binder, but with 10 aptamers connecting the virus to the star, we have a tight hold on the target.”

Once bound to the virus, the DNA star starts to fluoresce, making it easily visible in a blood test.

“Using designer DNA nanoarchitecture as a diagnostic is a first step,” Linhardt said.  “The next step would be to kill the virus once it’s bound. This can also be done by using a DNA origami nanoplatform, showing an even better biostability, to reconstruct a DNA star shape of aptamers. This is the first time people have used a DNA nanostructure this way, but the technology is broad, and we can expect to see it used in many other applications.”

This work was supported with funding from both the National Institutes of Health and the National Science Foundation. Wang is affiliated with the Holonyak Micro and Nanotechnology Laboratory.