Project description
Cracking the brain’s barrier with smart mRNA delivery
Getting treatments into the brain is one of medicine’s toughest puzzles. The blood-brain barrier (BBB) is a tightly controlled wall of cells. It shields our brains but also blocks many promising drugs. Supported by the Marie Skłodowska-Curie Actions programme, the PORTAL project is taking a fresh approach, inspired by the body’s own delivery system: apolipoproteins. These natural nanoparticles can cross the BBB. PORTAL is testing 400 apolipoprotein-based nanoparticles to find the best at delivering mRNA to brain cells in a model of neuroinflammation. Each one carries genetic barcodes to track its journey. By blending bioengineering and nanotech, PORTAL could pave the way for new mRNA therapies for brain disorders.
Objective
Efficient therapeutic delivery across the blood-brain barrier (BBB) remains a significant challenge in treating neurological disorders. The BBB, composed of tightly regulated endothelial cells, severely restricts drug access to the brain, reducing efficacy and increasing off-target effects. While lipid nanoparticles (LNPs) have been essential for developing mRNA-based vaccines, their use in brain-targeted therapies is limited by poor BBB penetration and suboptimal mRNA translation.
Apolipoproteins, our body’s own nanodelivery system, possess the inherent ability to cross the BBB. Extensive preliminary data demonstrate that apolipoprotein nanoparticles (aNPs) efficiently integrate mRNA for extrahepatic delivery and are a compelling platform for brain targeting. While mRNA immune cell delivery firmly established, I propose exploring apolipoprotein nanoparticles (aNPs) for mRNA delivery to the brain.
The PORTAL project aims to harness the unique properties of apolipoproteins to deliver mRNA across the BBB. By screening 400 compositionally diverse aNPs—comprising apolipoprotein A1, E, and fusion apolipoproteins targeting BBB receptors—this project seeks to identify lead candidates for effective mRNA delivery to the brain. Each aNP will carry mRNA encoding Cre recombinase, along with unique DNA barcodes for detailed biodistribution and functional studies in the A14 neuroinflammation mouse model.
By integrating protein engineering, RNA therapeutics, and preclinical neuroinflammation models, this research aims to uncover key factors driving BBB penetration and mRNA delivery efficiency. The innovative combination of apolipoproteins and lipid nanotechnology will unlock new pathways to the brain, setting a new standard for RNA-based treatments. Upon completion of this Program, I will be equipped with cutting-edge technical, teaching, and leadership skills, empowering me to excel as an independent researcher and drive innovation of nanomedicine brain treatments.
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.
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 genetics DNA
- medical and health sciences medical biotechnology nanomedicine
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics RNA
- engineering and technology nanotechnology nano-materials
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
5612 AE Eindhoven
Netherlands
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