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Synthesis of Multi-Silencing Polymerized RNA Nanoparticles for Enhanced Cardiac Transdifferentiation via Microneedle Delivery

Project description

Efficient transdifferentiation for optimal cardiac fibrosis therapies

Transdifferentiating cardiac fibroblasts into induced cardiomyocyte-like cells could overcome the limitations of traditional cardiac fibrosis therapies, which primarily manage symptoms rather than halting disease progression. However, current approaches face low transfection efficiency, uncontrolled gene expression and immune responses to viral vectors. With the support of the Marie Skłodowska-Curie Actions programme, the Multi-R-NPs project will enhance drug delivery by developing multi-silencing polymerised RNA nanoparticles (Multi-R-NPs) for personalised treatments. Using rolling circle transcription, the project will create Multi-R-NPs that facilitate unique combination therapies with multiple nucleic acid therapeutics. Microneedles will enable localised delivery, minimising side effects and overcoming barriers to cardiac treatment. This combined approach will promote optimal cardiac repair through efficient transdifferentiation.

Objective

My research aims to advance drug delivery by developing multi-silencing polymerized RNA nanoparticles (Multi-R-NPs) for customized treatments across a wide range of diseases, using engineered microneedles to enhance efficacy. This versatile platform can be adapted for applications such as stem cell differentiation and biosensing, with immediate potential to treat fibrotic diseases like cardiac and pulmonary fibrosis, reducing preventable mortality and improving patient quality of life. Therapeutic transdifferentiation of cardiac fibroblasts into induced cardiomyocyte-like cells could address the limitations of conventional cardiac fibrosis therapies, which typically only manage symptoms and do not prevent the progression of the disease. However, current transdifferentiation strategies face challenges such as low transfection efficiency, uncontrolled gene expressions, and immune responses to viral vectors. This proposal aims to develop multi-silencing polymerized RNA nanoparticles (Multi-R-NPs) through rolling circle transcription (RCT) to enable unique combination therapies that synergize multiple nucleic acid therapeutics. Moreover, to minimize the side effects of untargeted delivery and overcome barriers to cardiac delivery, we will use microneedles to enable local Multi-R-NP transfection. I anticipate that combining two state-of-the-art technologies, RCT and microneedles, will enable the delivery of synergistic nucleic acid therapeutics and promote more optimal cardiac repair through efficient transdifferentiation. During my fellowship at the University of Oxford in Professor Dame Molly Stevens’ lab, I will apply precise control polymerization of therapeutic RNAs and formulate multi-layered polyplex structures. The strong collaborative networks with the British Heart Foundation Centre for Research Excellence and the co-supervision of Prof. Stevens and Prof. Riley will bring out the full translational potential of this project.

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