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Design and development of exosomes with brush type architecture as RNA delivery vectors for active targeting of blood brain barrier (BBB)

Project description

Crossing the blood-brain barrier with polymer particles

MicroRNAs are non-coding RNAs with a key role in the regulation of gene expression. Disturbance of microRNA levels has been associated with many diseases, including neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. The EU-funded ExoBBB project proposes to employ microRNAs to restore perturbed gene expression and modulate brain function. Researchers will use macromolecular structures as microRNA delivery vehicles to the brain across the blood-brain barrier. The properties of the structures can be fine-tuned to modify their brain targeting for the required gene expression.

Objective

MicroRNAs (miRs) are identified as significant regulators in modulating brain functions in central nervous system (CNS) disorders like Alzheimer’s disease (AD), Huntington’s and Parkinson’s disease (PD) and amyotropic lateral sclerosis. Sustained delivery of miRNAs to brain could be an excellent strategy to regulate gene expressions affected in the progressive neurodegenerative diseases. Highly biocompatible nanocarriers like extracellular vesicles (eg: exosomes) are an excellent choice as delivery vehicles for miRs but their short half life in systemic circulation and difficulty in crossing BBB limits the application. ExoBBB proposes to use high density polymer brushes to maximise RNA capture and stability, confer biofunctionality, stealth behaviour and active targeting to CNS. Density and chemical composition of these polymer brushes can be tuned precisely to attain optimum physicochemical features necessary for active targeting of BBB. Grafting of polymer brushes over exosomes can impart a star shaped architecture which in turn has been proven effective for neuronal targeting. In addition, these brushes can offer abundant surface functionalities for the conjugation of active targeting ligands. Dual targeting ability of the polymer brush chains will be evaluated by surface modification with peptides which can actively target BBB and neurons. The aim of ExoBBB is to design highly stable and efficient cationic polymer brush-based RNA delivery vectors that can be grafted on safe and biocompatible nanoparticles like exosomes for brain targeting and regulation of neuronal cell phenotype for prolonged periods of time.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

CENTRO DE NEUROCIENCIAS E BIOLOGIACELULAR ASSOCIACAO
Net EU contribution

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.

€ 159 815,04
Address
UNIVERSIDADE DE COIMBRA LARGO MARQUES DE POMBAL
3004 517 Coimbra
Portugal

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 159 815,04
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