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

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 labs 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)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences biochemistry biomolecules proteins proteomics
• natural sciences physical sciences optics microscopy
• medical and health sciences medical biotechnology nanomedicine
• natural sciences biological sciences genetics RNA
• engineering and technology nanotechnology nano-materials

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Lipid Nanoparticles
• mRNA-LNPs
• RNA therapeutics
• Cryo-electron microscopy
• LNP morphology
• LNP trafficking
• nanostructure analysis
• gene delivery

Coordinator