DNA meshes effectively target the spike protein and detect the COVID-19 virus at very low levels

Tiny webs woven from strands of DNA can ensnare the spike protein of the virus that causes COVID-19, make the virus glow for a quick yet sensitive diagnostic test — and also prevent the virus from closing cells infect, opening up a new possible avenue to antiviral treatment, according to a new study.

University of Illinois Urbana-Champaign researchers and collaborators demonstrated the ability of DNA networks to detect and prevent COVID-19 in human cell cultures in a paper published in the Journal of the American Chemical Society.

“This platform combines the sensitivity of PCR with the speed and low cost of antigen testing,” said study leader Xing Wang, professor of bioengineering and chemistry at Illinois University. “We need tests like this for a number of reasons. One is to prepare for the next pandemic. The other reason is to follow ongoing virus epidemics – not just coronaviruses, but other deadly and economically important viruses like HIV or influenza.”

DNA is best known for its genetic properties, but it can also be folded into tailored nanoscale structures that can perform functions or specifically bind to other structures, much like proteins. The DNA webs developed by the Illinois group were engineered to attach to the coronavirus spike protein – the structure that protrudes from the virus’s surface and attaches to receptors on human cells to infect them. Once tied, the webs emit a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.

The researchers showed that their DNA nets effectively targeted the spike protein and were able to detect the virus at very low levels, matching the sensitivity of gold-standard PCR tests, which can take a day or more to detect Deliver results from a clinical laboratory.

The technique has several advantages, Wang said. It requires no special preparation or equipment and can be performed at room temperature, so all a user needs to do is mix the sample with the solution and read it. The researchers estimated in their study that the method would cost $1.26 per test.

“Another advantage of this measure is that we can detect and distinguish the whole virus that is still infectious from fragments that may no longer be infectious,” Wang said. Not only does this give patients and doctors a better understanding of whether they are contagious, but it could also significantly improve modeling and tracking of active community-level outbreaks, such as through sewage.

In addition, the DNA networks inhibited the spread of the virus in live cell cultures, with antiviral activity increasing with the size of the DNA network scaffold. This points to the potential of DNA structures as therapeutics, Wang said.

“I had this idea at the very beginning of the pandemic to build a platform to test but also to inhibit at the same time,” Wang said. “Many other groups working on inhibitors are trying to wrap up the whole virus or the parts of the virus that provide access to antibodies. This is not good because you want the body to make antibodies. With the hollow DNA mesh structures, antibodies can still access the virus.”

The DNA mesh platform can be adapted to other viruses, Wang said, and even multiplexed so a single test could detect multiple viruses.

“We are trying to develop a unified technology that can be used as a plug and play platform. We want to take advantage of the high binding affinity, low detection limit, low cost and quick preparation of DNA sensors,” Wang said.

The National Institutes of Health supported this work through the Rapid Acceleration of Diagnostics program. Researchers will continue to work through the RADx program to explore and accelerate clinical applications for the DNA mesh platform.

Wang is also associated with the Holonyak Micro and Nanotechnology Lab and the Carl R. Woese Institute for Genomic Biology in Illinois.

Source:

University of Illinois at Urbana-Champaign

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