Fishing for Viruses with DNA Nanobait

Respiratory tract infections are one of the leading causes of deaths from infectious diseases worldwide – but many viruses have similar symptoms, making it more challenging to choose the appropriate treatment. Using self-assembled DNA “nanobait” that can simultaneously detect multiple short RNA targets, a new test can identify different common respiratory viruses using a single sample (1).

For those of us who are unfamiliar with the concept of DNA nanobait, I asked senior author Ulrich F. Keyser from the University of Cambridge to give us the lowdown: “We can use DNA to build small structures – like molecular Lego,” he says. “Viruses use RNA to store their genetic code – and RNA is chemically compatible with DNA, so we can use DNA to build a nanobait that only binds to RNA originating from one virus, such as SARS-CoV-2.”

When asked what inspired his team to develop a test able to simultaneously identify multiple viruses and variants, Keyser says, “During the COVID-19 lockdown, we started to work on a viral RNA test and our co-author Stephen Baker, Principal Research Associate at the University of Cambridge, pointed out that one main issue was to be able to distinguish different viruses as quickly as possible.”

In terms of SARS-CoV-2, the nanobait was able to accurately determine whether SARS-CoV-2 was present or absent in samples taken from patient oropharyngeal swabs. But as well as concurrently identifying different viruses, the nanobait can be easily reprogrammed to distinguish between SARS-CoV-2 variants, for example, with single-nucleotide resolution.

Importantly, the technology is able to detect viral RNA without the time-consuming or convoluted steps that gold-standard tests, such as PCR, require. Moreover, although highly accurate, PCR tests can only test for one virus at a time and can take hours to deliver results. In contrast, the nanobait test returns highly accurate results in under an hour. The test also offers high specificity and sensitivity because it can detect multiple targets from the same viral RNA, as demonstrated when detecting SARS-CoV-2 in clinical samples.

Rapidly testing for viral RNA could also play a role in treatment selection – particularly when infections could be caused by two different types of pathogens. Keyser and his team are currently working on this endeavor; “A test that can tell if a patient has a bacterial or viral infection in a couple of hours could help streamline and improve patient care,” says Keyser. “Furthermore, if one can tell which virus it is, the appropriate medication can be easily chosen – and, in terms of antimicrobial resistance, if the infection is not viral and one can tell what bacterial infection it is, healthcare workers can choose the correct antibiotic, potentially reducing the prescription of antimicrobial drugs.”

Next on the agenda for Keyser is to develop a similar test that can be used in low- and middle-income countries, which he plans to collaborate on with Baker. It’s this collaborative and curious nature that led him here in the first place. “This work was enabled by fundamental, curiosity-driven research over the past 15 years in my Cambridge lab,” Keyser highlights. “Combining our knowledge with the expertise of people in different fields allowed us to move fast and go far beyond the original goal of a test for COVID-19.”