Summary
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.
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| Web resources: | https://cordis.europa.eu/project/id/101063372 |
| Start date: | 01-09-2023 |
| End date: | 31-08-2025 |
| Total budget - Public funding: | - 165 312,00 Euro |
Cordis data
Original description
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.Status
SIGNEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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