The projects are supported as part of ARIA's Sustained Viral Resilience programme, a £57 million initiative led by Programme Director Brian Wang. In this programme, 11 funded teams will explore and unlock ways to create sustained innate immunoprophylactics (SIIPs) - a new class of medicines that provide durable, broad-spectrum protection against respiratory viruses by engineering the innate immune system.
Viruses are a large and diverse group of microorganisms, causing diseases that often affect the respiratory tract – ranging from the common cold to COVID-19 – and posing a continued risk of pandemic outbreaks. Viral infections also impose a substantial economic burden in the UK and worldwide, with the COVID-19 pandemic estimated to have cost the global economy more than £10tn.
Developing "smart" DNA medicine to prevent respiratory infections
One of the three projects at the University of Oxford will be led by Professor Mark Coles at the Kennedy Institute.
The iGATE project aims to develop a new class of "smart" DNA medicines based on programmable synthetic biosensors. These biosensors are designed to remain inactive in healthy tissue but switch on in response to viral infection. The approach involves engineering compact gene "circuits" – inspired by how neural circuits process information – that can detect molecular signs of infection and activate targeted antiviral defences.
The project brings together researchers from across the University of Oxford, in collaboration with Professor Ron Weiss and Majo Duran at the Massachusetts Institute of Technology. By combining synthetic biology with artificial intelligence, the team will design and optimise gene circuits that can sense infection-related signals in respiratory cells and respond in a precise, controlled way. Importantly, these systems are intended to activate only when needed, reducing the risk of unnecessary inflammation while maintaining effective protection.
"The iGATE team combines world-leading expertise in bioengineering at MIT and respiratory infection research at the University of Oxford to develop a next-generation "smart" DNA medicine. This approach aims to strengthen early immune defences against both seasonal respiratory infections and emerging, unknown pandemic threats. If successful, it could offer a fundamentally new strategy for reducing the impact of future pandemics," said Mark.
The platform will use modular "plug-and-play" components, allowing different sensors and therapeutic effectors to be combined to address a range of viruses. The technology will be tested and refined in human airway models to ensure both safety and efficacy, with a strong emphasis on minimising unintended effects. In parallel, the team will develop delivery methods that introduce these DNA circuits without triggering unwanted immune responses.
Professor Dame Molly Stevens, one of the iGATE team co-leads at Oxford said: "We are delighted to develop advanced delivery technologies for the iGATE project and excited by the ambition and potential impact of the project."
Overall, iGATE aims to create a next-generation, self-regulating approach to strengthen the body's early defences against respiratory infections and reduce the risk of severe disease and hospitalisation.
"Synthetic biology and immunology have each been advancing rapidly on their own. What excites us about this project is what happens when they truly intersect. For the first time, we can bring circuits with the modularity, specificity, and gradient-processing complexity that synthetic biology offers into the innate immune system. The line between a protective and a harmful innate immune response is very fine, and having the tools to intervene precisely is what draws us to this project," said Majo Duran, a project co-lead at MIT.
The other two projects at Oxford are led by Paul Klenerman at the Nuffield Department of Medicine (NDM) and Jan Rehwinkel at the MRC Weatherall Institute of Molecular Medicine (WIMM) in the Radcliffe Department of Medicine (RDM). These projects will draw on skills and expertise from collaborators across the University, and beyond, with Molly Stevens from the Department of Physiology, Anatomy and Genetics playing an important role in all three projects.
Read the full story on the University of Oxford website.