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Engineering fibroblast-targeted mRNA therapies as clinically-focused adjuvants for unlocking tissue regeneration in arthritis

Project description

Reprogramming synovial cells to restore joint health

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and progressive destruction of joints, leading to pain and disability. Current first-line therapy involves disease-modifying anti-rheumatic drugs (DMARDs) that manage inflammation but cannot repair damaged tissue. With the support of the Marie Skłodowska-Curie Actions programme, the Nano-Synergy project aims to develop mRNA-based nanodelivery systems to reprogramme synovial cells that line the inner part of the joints and are responsible for joint lubrication and nourishment. Researchers will test the combination of targeted mRNA therapy with existing DMARDs in human organoid models and animal models as a regenerative treatment for RA.

Objective

As a Marie Skłodowska-Curie (MSC) fellow, I aim to engineer clinically focused mRNA formulations for rewriting the biology of synovial cells and unlocking regeneration in rheumatoid arthritis, and expand the capabilities of current Disease Modifying Anti-Rheumatic Drugs (DMARDs). The current first-line therapies for rheumatoid arthritis (RA), DMARDs, effectively manage inflammation but do not regenerate destroyed bone tissue, leading to lifelong disability and pain. We hypothesize that reprogramming specific synovial cell types by combining targeted mRNA delivery with approved DMARD therapies can restore the pathological tissue state in arthritis back to a healthy state and enable long-term joint repair. This project, Nano-Synergy, will be supervised by global leader in materials chemistry and tissue engineering Prof. Dame Molly Stevens at the Kavli Institute for Nanoscience Discovery (University of Oxford). I will collaborate with tissue biologists Prof. Chris Buckley and Prof. Mark Coles at the Kennedy Institute of Rheumatology (University of Oxford), the world’s premiere rheumatology research centre. In the host Stevens group, I will rationally engineer mRNA nanodelivery systems which specifically deliver payloads to joint synovial cells by using bio-orthogonal chemistry and revolutionary techniques for characterizing nanoparticle physicochemical properties. I will demonstrate that mRNA synergizes with DMARDs to reprogram arthritis at the cellular level by adapting a state-of-the-art organoid system utilized by Buckley and Coles which spatially and transcriptionally recapitulates human arthritis, and then demonstrate tissue regeneration using an animal model. In summary, as a biomedical engineer and immunologist trained in RNA delivery and animal models of tissue injury, I will integrate unrivalled expertise and capabilities in engineering and rheumatology at Oxford to pioneer new regenerative therapies.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 260 347,92
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom
Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost
No data