Descrizione del progetto
Attraversare la barriera emato-encefalica con le particelle polimeriche
I microRNA sono RNA non codificanti che svolgono un ruolo chiave nella regolazione dell’espressione genica. L’alterazione dei livelli di microRNA è stata correlata a varie malattie, tra cui disturbi neurodegenerativi quali la malattia di Alzheimer e il morbo di Parkinson. Il progetto ExoBBB, finanziato dall’UE, propone l’impiego di microRNA per ripristinare l’espressione genica perturbata e modulare la funzione cerebrale. I ricercatori impiegheranno strutture macromolecolari come vettori per apportare microRNA al cervello attraverso la barriera emato-encefalica. Le proprietà di queste strutture possono essere messe a punto per modificare il loro intervento sul cervello secondo l’espressione genica richiesta.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
3004 517 Coimbra
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