Targeting lung inflammation at source: gene therapy approach shows promise in severe respiratory disease
Researchers from the Department of Pathology have developed a targeted gene delivery platform that enables localised control of immune responses in the lung, offering a potential new strategy for treating severe respiratory inflammation.
In a new study published in Science Immunology, the team demonstrates that an adeno-associated viral vector (AAV6.2-CC10) can deliver anti-inflammatory cytokines directly to lung tissue, driving sustained, local production without detectable systemic effects. This approach addresses a longstanding challenge in immunotherapy: how to harness potent cytokines while avoiding widespread immune suppression or toxicity.
Using preclinical models, the researchers show that lung-restricted expression of cytokines such as IL-1 receptor antagonist (IL-1RA), IL-10 and IL-2 can reshape the local immune environment. Notably, IL-1RA delivery improved lung function and reduced tissue damage during influenza infection, while all three cytokines significantly mitigated pathology in a clinically relevant model of influenza-associated pulmonary aspergillosis.
The study highlights the importance of spatially targeted immunomodulation. Rather than altering systemic immunity, the platform acts directly within the lung microenvironment—reducing harmful inflammation while preserving antiviral responses.
Although further work is needed to translate these findings into human systems, the results provide a compelling proof of concept for tissue-specific delivery of biologics. The platform could have broad applications across respiratory diseases where immune-mediated damage drives pathology.