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Revealing the RNA-LNP ultrastructure and subcellular trafficking using advanced Cryo-electron microscopy and proteomics

Project description

Advanced nanoparticles for RNA delivery

RNA therapeutics use RNA molecules to regulate, replace, or introduce gene functions in the body, offering powerful new ways to treat diseases that were previously considered untreatable. This technology relies on lipid nanoparticles (LNPs) to protect RNA and deliver it safely into cells. However, less than 10 % of administered RNA reaches the cytoplasm. With the support of the Marie Skłodowska-Curie Actions programme, the CryoLipNano project will investigate the role of LNP composition, structure and integrity on their intracellular trafficking and delivery efficiency. Using state-of-the-art techniques, researchers will study the relationship between lipid composition, LNP morphology and RNA localisation after endocytosis. These insights are expected to pave the way for more potent LNPs.

Objective

RNA therapeutics are revolutionizing medicine, offering new treatment possibilities for diseases once considered undruggable. Central to the delivery of nucleic acids, especially mRNA, is the use of Lipid Nanoparticles (LNPs) – the most advanced and the only clinically approved gene delivery platform. LNPs protect mRNA from degradation, facilitate its transfer, and ensure delivery into the cell. Despite their potential, the therapeutic potency of RNA-LNPs remains limited due to suboptimal RNA delivery, with <10% of the administered RNA-LNP system reaching the cytoplasm. To this end, crucial gaps persist in our understanding of LNP structure, integrity and their impact on trafficking and RNA delivery. CryoLipNano aims to advance our knowledge on LNP ultrastructure and intracellular dynamics, by linking – for the first time – lipid composition, morphology, LNP integrity, mRNA localization and trafficking after endocytosis. By integrating physical chemistry with cutting-edge cryo-electron microscopy (cryoEM), advanced imaging techniques, and proteomic analysis, this study will address critical knowledge gaps, ultimately leading to the rational design of second-generation LNP platforms with enhanced efficiency and potency. Moreover, CryoLipNano will establish the first RNA-LNP research hub at the host institute and, alongside with the ERA Chair's launch of the country's first cryoEM facility, will create a new line of expertise in RNA-LNP characterization by cryoEM. This expertise will be valuable not only in Greece, but also for entities across Europe and globally. CryoLipNano will also focus on disseminating the lab’s presence, educating the scientific community and the public about RNA therapeutics and their structural analysis, and inspiring young scientists. Finally, the high-level science and training the fellow will receive, will significantly advance her expertise and enhance her future employability in the field of nanomedicine and RNA therapeutics.

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

ETHNIKO IDRYMA EREVNON
Net EU contribution
€ 197 263,68
Address
VAS KONSTANTINOU 48
116 35 ATHINA
Greece
Region
Αττική Aττική Κεντρικός Τομέας Αθηνών
Activity type
Research Organisations
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Total cost
No data