A schematic showing the new DNA nanobait technology and associated experimental procedure.
Ulrich Keyser and his team designed their DNA nanobait technology to hunt down short viral RNA targets directly from patient samples.

Viral infections spread fast, but detection methods lag behind. Now, researchers at Cambridge University developed a novel nanotechnology that simultaneously detects multiple viruses directly from a small sample volume, which they hope will make a splash in rapid diagnostics.1

Ulrich Keyser, a biophysicist from Cambridge University and coauthor of the paper, previously used nanopore sensors to detect isolated short nucleic acid species.2 Like an electrocardiogram recording electrical signals from the heart, nanopore sensors transform biological signals into electrical currents. When molecules swim through the nanopore’s ionic current, they create ripples that carry information about their identities.

To adapt this technology for diagnostics, the team developed a one-pot approach that starts with the enzyme ribonuclease H, guided by DNA oligos, to selectively cut short sections of RNA that uniquely identify specific viruses.

To catch these viral RNA fragments, Keyser and his team developed DNA nanobaits. Using single-stranded bacteriophage DNA like a fishing rod, the researchers hung multiple lines baited with bespoke complementary DNA oligos, or nanobaits, bound to bulky placeholder oligos. Drawn to their complementary nanobaits, viral RNAs displaced the larger placeholder oligos and bound to the bait.

As the baited fishing rod flew through the nanopore sensor, it displaced ions, with larger molecules creating larger ripples in the ionic current. Unlike previous efforts that use additive signals for viral detection, Keyser’s approach causes a reduction in signal. “That is not only really innovative, but can be very powerful diagnostically because it reduces false positives,” said Adam Hall, a biomedical engineer at Wake Forest University School of Medicine who was not involved in the study.

The researchers used DNA nanobaits to fish for different respiratory viruses, including SARS-CoV-2 variants. “The nice thing about the test is that by adding more oligos, you can select for more pieces of the same viral genome for variant detection, or you can detect different viruses,” said Keyser.