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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.
Sustained protection through innate immune activation
Professor Jan Rehwinkel’s project will focus on harnessing MDA5, a key sensor in the innate immune system, to develop new prophylactic treatments capable of protecting against many different respiratory viruses.
The innate immune system is a complex network that protects against infections, including viruses. Previous discovery research by the Rehwinkel Group found that specialised proteins such as MDA5 have a key role in kick-starting the innate immune response – detecting viral or unusual RNA and triggering antiviral defences.
In this ARIA-funded project, researchers will design synthetic RNA molecules that activate MDA5, mimicking infection signals to stimulate a broad immune response. These RNA agonists will be delivered using DNA-based systems designed to target respiratory tissues.
The aim is to create a treatment that, after a single administration, could provide sustained protection against multiple respiratory viruses. The approach will be tested across cell models, human airway organoids and animal systems, against viruses such as influenza, SARS-CoV-2 and respiratory syncytial virus.
Speaking about the new funding, Jan Rehwinkel, Professor of Innate Immunology at the MRC WIMM, said:
We are deeply motivated by and excited about the unique possibilities ARIA funding unlocks to achieve a paradigm shift in the control of viral infections. The current clinical status quo – pathogen-specific vaccines and treatments – remains perpetually a step behind emerging threats, as evidenced by the recent SARS-CoV-2 pandemic.
ARIA’s vision of sustained, broad-spectrum resilience is ambitious, yet we believe it is achievable by harnessing one of the very mechanisms that have protected our species through eons of viral evolution: the MDA5 pathway. By coupling this innate signalling pathway with cutting-edge synthetic biology and delivery engineering, we aim to build a prophylactic that we hope to be effective not just against known viruses, but also against those yet to emerge.
Learn more about the Oxford-led projects funded by ARIA’s Sustained Viral Resilience Programme.
Learn more about the Rehwinkel Group's research: