Tiny networks woven from strands of DNA can infect the spiky protein of the virus that causes COVID-19, illuminating the virus for a rapid and sensitive diagnostic test—and also blocking the virus from infecting cells, opening up a potential new avenue for antivirals. Treatment according to a new study.
Researchers at the University of Illinois, Urbana-Champaign and collaborators demonstrate the ability of DNA networks to detect and disrupt COVID-19 in human cell cultures in a research paper published in the Journal of the American Chemical Society.
“This platform combines the sensitivity of polymerase chain reaction (PCR) with the speed and low cost of antigen tests,” said study leader Xing Wang, professor of bioengineering and chemistry at Illinois. “We need tests like this for two reasons. One is to prepare for the next pandemic. The other reason is to track ongoing viral epidemics – not only coronaviruses, but also other deadly and economically impactful viruses like HIV or influenza.”
DNA is best known for its genetic properties, but it can also be folded into custom nanostructures that can perform functions or bind specifically to other structures just as proteins do. The DNA networks developed by the Illinois group are designed to bind to the coronavirus spike protein — the structure that protrudes from the surface of the virus and attaches to receptors on human cells to infect it. Once attached, the nets emit a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.
The researchers showed that their DNA networks effectively targeted the spike protein and were able to detect the virus at very low levels, equivalent to the sensitivity of gold standard PCR tests that can take a day or more to return results from a clinical laboratory.
Wang said this technology has many advantages. It requires no preparation or special equipment, and can be made at room temperature, so all the user will do is mix the sample with the solution and read it. In their study, the researchers estimated that the method would cost $1.26 per test.
“Another advantage of this procedure is that we can detect the whole virus, which is still infectious, and distinguish it from fragments that may not be infectious anymore,” Wang said. This not only gives patients and clinicians a better understanding of whether they are contagious, but could greatly improve community-wide modeling and tracking of active outbreaks, such as wastewater.
In addition, DNA networks inhibited viral spread in live cell cultures, with antiviral activity increasing as the size of the DNA scaffold network increased. Wang said this indicates the potential of DNA structures as therapeutic agents.
“I came up with this idea at the beginning of the epidemic to build a platform for testing, but also for prevention at the same time,” Wang said. “A lot of other groups working on inhibitors are trying to wrap the whole virus around, or the parts of the virus that provide access to the antibodies. That’s not good, because you want the body to form antibodies. With hollow DNA network structures, the antibodies can still reach virus.”
The DNA network platform can be adapted to other viruses, Wang said, and can even be multiplexed so that a single test can detect multiple viruses.
“We are trying to develop a standardized technology that can be used as a plug-and-play platform. We want to take advantage of the high interconnection affinity of DNA sensors, low detection limit, low cost, and fast setup,” said Wang. .
The National Institutes of Health supported this work through the Rapid Diagnosis Acceleration Program. The researchers will continue to work through the RADx program to explore and accelerate clinical applications of the DNA network platform.
Wang is also affiliated with the Holonyak Micro and Nanotechnology Laboratory and the Carl R. Woese Institute for Genomic Biology in Illinois.
University of Illinois at Urbana-Champaign