Tiny nets woven from DNA strands can
ensnare the spike protein of the virus that causes COVID-19,
lighting up the virus for a fast-yet-sensitive diagnostic test --
and also impeding the virus from infecting cells, opening a new
possible route to antiviral treatment, according to a new
study.
Researchers at the University of Illinois Urbana-Champaign and
collaborators demonstrated the DNA nets' ability to detect and
impede 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 and the speed and
low cost of antigen tests," said study leader Xing Wang, a
professor of bioengineering and of chemistry at Illinois. "We need
tests like this for a couple of 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 also can be
folded into custom nanoscale structures that can perform functions
or specifically bind to other structures much like proteins do. The
DNA nets the Illinois group developed were designed to bind to the
coronavirus spike protein -- the structure that sticks out from the
surface of the virus and binds to receptors on human cells to
infect them. Once bound, the nets give off a fluorescent signal
that can be read by an inexpensive handheld device in about 10
minutes.
The researchers demonstrated that their DNA nets 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
lab.
The technique holds several advantages, Wang said. It does not
need any special preparation or equipment, and can be performed at
room temperature, so all a user would 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 the
entire virus, which is still infectious, and distinguish it from
fragments that may not be infectious anymore," Wang said. This not
only gives patients and physicians better understanding of whether
they are infectious, but it could greatly improve community-level
modeling and tracking of active outbreaks, such as through
wastewater.
In addition, the DNA nets inhibited the virus's spread in live
cell cultures, with the antiviral activity increasing with the size
of the DNA net scaffold. This points to DNA structures' potential
as therapeutic agents, Wang said.
"I had this idea at the very beginning of the pandemic to build
a platform for testing, but also for inhibition at the same time,"
Wang said. "Lots of other groups working on inhibitors are trying
to wrap up the entire virus, or the parts of the virus that provide
access to antibodies. This is not good, because you want the body
to form antibodies. With the hollow DNA net structures, antibodies
can still access the virus."
The DNA net platform can be adapted to other viruses, Wang said,
and even multiplexed so that a single test could detect multiple
viruses.
"We're trying to develop a unified technology that can be used
as a plug-and-play platform. We want to take advantage of DNA
sensors' high binding affinity, low limit of detection, low cost
and rapid preparation," Wang said.
The National Institutes of Health supported this work through
the Rapid Acceleration of Diagnostics program. The researchers will
continue to work through the RADx program to explore and accelerate
clinical applications for the DNA net platform.
Wang also is affiliated with the Holonyak Micro and
Nanotechnology Lab and the Carl R. Woese Institute for Genomic
Biology at Illinois.
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