Description du projet
Un nouveau système de transport membranaire des acides nucléiques favorisera l’innovation dans le domaine des thérapies à base d’acides nucléiques
Les acides nucléiques, dont l’ADN et l’ARN, jouent un rôle essentiel dans toutes les cellules, et dans les virus. Les thérapies à base d’acides nucléiques exploitent ces molécules pour traiter les maladies en ciblant la «machinerie» correspondante in vivo. Cependant, leur administration dans des solutions aqueuses classiques est entravée par des problèmes d’efficacité et de stabilité. Les solvants eutectiques profonds (DES pour «deep eutectic solvents»), une nouvelle classe prometteuse de mélanges non aqueux bon marché aux propriétés physico-chimiques ajustables, pourraient surmonter ces problèmes s’ils parviennent à transporter efficacement les acides nucléiques à travers les membranes cellulaires. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet DUNE synthétisera des DES présentant différentes propriétés pertinentes pour le transport et étudiera leur capacité à faciliter le transport membranaire d’acides nucléiques.
Objectif
The delivery of nucleic acids as therapeutic methods holds great potential to provide new treatments against emergent pathogens and important diseases. However, the development of functional therapies is often hindered by the poor efficiency and stability of the current transport technologies. Deep eutectic solvents (DES) are non-aqueous sustainable liquids obtained through the combination of simple organic molecules. The physicochemical properties of the DES can be tailored through the selection of their constituents, to optimally perform in specific applications. DES have been recently shown to increase the stability and activity of nucleic acids (NA), as compared to those in aqueous systems. Despite the excellent and encouraging physicochemical properties of DES, these solvents have not been investigated, to date, for the transport of NA across cell membranes. This project will finally fill the knowledge gap that exists between the promising properties of DES and their potential ability to selectively deliver NA into the cell cytosol. Here, a combinatorial approach will be used to synthesise a library of DES with different properties relevant for transport (e.g. amphiphilicity and charge density). The ability of these to enable membrane transport of NA will be investigated as a function of the system properties. The exclusive properties of the DES solvent will go beyond the state-of-the-art, as they will allow: i) fine-tuning of DES/cargo interactions and binding strength by DES counterion adjustment; ii) precise hydrophobic DES control for membrane partition regulation; iii) enhanced physicochemical stability of the resulting particles and simpler synthetic and scaling up methodology, as well as reduced production costs. Overall, this project is aimed to discover a completely new range of potential applications of DES in membrane transport and biomolecular cargo preservation, which will open a new research field of potential applications in NA delivery.
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Appel à propositions
(s’ouvre dans une nouvelle fenêtre) HORIZON-MSCA-2021-PF-01
Voir d’autres projets de cet appelRégime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
15782 Santiago De Compostela
Espagne