Simultaneous identification of viruses and viral variants with programmable DNA nanobait

Publication: Nature Nanotechnology

Filip Bošković, Jinbo Zhu, Ran Tivony, Alexander Ohmann, Kaikai Chen, Mohammed F. Alawami, Milan Đorđević, Niklas Ermann, Joana Pereira Dias, Michael Fairhead, Mark Howarth, Stephen Baker, Ulrich F. Keyser

16 January 2023


Respiratory infections are the major cause of death from infectious disease worldwide. Multiplexed diagnostic approaches are essential as many respiratory viruses have indistinguishable symptoms.

We created self-assembled DNA nanobait that can simultaneously identify multiple short RNA targets. The nanobait approach relies on specific target selection via toehold-mediated strand displacement and rapid read-out via nanopore sensing. Here, we show this platform can concurrently identify several common respiratory viruses, detecting a panel of short targets of viral nucleic acids from multiple viruses.

Our nanobait can be easily reprogrammed to discriminate viral variants, as we demonstrated for several key SARS-CoV-2 variants with single-nucleotide resolution. Lastly, we show that nanobait discriminates between samples extracted from oropharyngeal swabs from negative and positive SARS-CoV-2 patients without pre-amplification.

Our system allows for multiplexed identification of native RNA molecules, providing a new scalable approach for diagnostics of multiple respiratory viruses in a single assay.

View publications

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Publication: Nature Genetics

Praveen Surendran, Joanna M. M. Howson et al

23 November 2020


Increased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and related disability worldwide. Identifying biological pathways associated with blood pressure is important to understand the aetiology of CVD.

In this study involving collaborators from across the globe, and participants from diverse ancestries, researchers investigated whether genetic variants that a small proportion of people carry have an impact on blood pressure regulation and more readily implicate the genes underlying blood pressure regulation.

They identified 87 such genetic variants influencing blood pressure regulation that only a small proportion of people carry. In addition to identifying novel candidate genes associated with blood pressure, they showed a potential link between foetal development and an inverse relationship between systolic and diastolic blood pressure with stroke.

As shown in this study, a complex outcome like blood pressure requires large sample sizes to detect genetic variation associated with blood pressure that are rare in humans; studies to date have mainly looked at genetic variants that are carried by many people and therefore have very small effects on blood pressure regulation.

This study contributes to a significant improvement in researchers’ understanding of key genes controlling a risk factor like BP so they can better understand complex diseases like CVD and help identify new blood pressure therapies.

View publication

COVID-19 and Pneumothorax: A Multicentre Retrospective Case Series

Publication: European Respiratory Journal

Anthony W. Martinelli, Tejas Ingle, Joseph Newman, Iftikhar Nadeem, Karl Jackson, Nicholas D. Lane, James Melhorn, Helen E. Davies, Anthony J. Rostron, Aldrin Adeni, Kevin Conroy, Nicholas Woznitza, Matthew Matson, Simon E. Brill, James Murray, Amar Shah, Revati Naran, Samanjit S. Hare, Oliver Collas, Sarah Bigham, Michael Spiro, Margaret M. Huang, Beenish Iqbal, Sarah Trenfield, Stephane Ledot, Sujal Desai, Lewis Standing, Judith Babar, Razeen Mahroof, Ian Smith, Kai Lee, Nairi Tchrakian, Stephanie Uys, William Ricketts, Anant R.C. Patel, Avinash Aujayeb, Maria Kokosi, Alexander J.K. Wilkinson, Stefan J. Marciniak

10 September 2020


Summary

Pneumothorax and pneumomediastinum have both been noted to complicate cases of COVID-19 requiring hospital admission. The research team reported the largest case series yet described of patients with both these pathologies that includes non-ventilated patients.

Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival.

Seventy-one patients from 16 centres were included in the study, of whom 60 patients had pneumothoraces (six also with pneumomediastinum), whilst 11 patients had pneumomediastinum alone.

Survival at 28 days was not significantly different following pneumothorax or isolated pneumomediastinum. The incidence of pneumothorax was higher in males. The 28-day survival was not different between the sexes. Patients above the age of 70 had a significantly lower 28-day survival than younger individuals.

These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and the researchers encourage active treatment to be continued where clinically possible.

Anthony Martinelli and Margaret Huang are supported by the Wellcome Trust. Stefan Marciniak is supported by the Medical Research Council, NIHR Cambridge BRC, Royal Papworth Hospital and the Alpha1-Foundation.

Click to read: Punctured lung affects almost one in a hundred hospitalised COVID-19 patients

View publication

© Copyright - NIHR Cambridge Biomedical Research Centre 2025