Descripción del proyecto
Atravesar la barrera hematoencefálica con partículas poliméricas
Los microARN son ARN no codificantes con una función fundamental en la expresión génica. Las perturbaciones en los niveles de microARN se han asociado con múltiples enfermedades, entre las que se incluyen trastornos neurodegenerativos como la enfermedad de Alzheimer y la enfermedad de Parkinson. El proyecto financiado con fondos europeos ExoBBB se propone emplear microARN para restaurar la expresión génica perturbada y modular la función encefálica. Los investigadores utilizarán estructuras macromoleculares como vectores del microARN al encéfalo a través de la barrera hematoencefálica. Las propiedades de las estructuras pueden ajustarse para modificar su diana encefálica para la expresión génica requerida.
Objetivo
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.
Ámbito científico
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Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
3004 517 Coimbra
Portugal