Project description
A novel nucleic-acid membrane-transport system will foster innovation in nucleic acid therapeutics
Nucleic acids including DNA and RNA play essential roles in all cells – and in viruses. Nucleic acid therapeutics harness these molecules to treat diseases by targeting related ‘machinery’ in vivo. However, their delivery in conventional aqueous solutions is hindered by challenges in efficiency and stability. Deep eutectic solvents (DESs), a promising new class of inexpensive, non-aqueous mixtures with tuneable physicochemical properties, could overcome these issues if they can effectively transport nucleic acids across cell membranes. With the support of the Marie Skłodowska-Curie Actions programme, the DUNE project will synthesise DESs with different properties relevant for transport and investigate their ability to enable membrane transport of nucleic acids.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
15782 Santiago De Compostela
Spain