Summary
Application of pulsed electric field (PEF) can reversibly increase the permeability of the cell membrane allowing the access of otherwise impermeable DNA molecules to the inside of the cell. Introduction of foreign DNA molecules encoding immuno-modulatory proteins, antibodies and antigens into cells using PEF, known as Gene Electro-Transfer (GET), is increasingly used for the modulation of the immune system or immunotherapy. While GET based immunotherapy presents itself as a potent application for treatment of cancer and vaccination against infectious diseases, it is suffering from low levels of transgene expressions in vivo. This low efficiency can largely be attributed to our lack of fundamental understanding of the mechanisms by which DNA molecules overcome the barriers of the extra-cellular matrix and the cell membrane in the presence of an electric field. In this action, I aim to provide this required fundamental understanding using principles of polymer physics, soft matter and statistical mechanics. Experiments based on these principles will be conducted in vitro and in vivo to generate results that can be directly compared to theories and models of DNA transport through the extra-cellular matrix and the cell membrane. Understanding the mechanisms within the frameworks of polymer physics will radically improve the efficiency of GET immunotherapy, because it will provide a mechanistic ground for developing optimum protocols within complex tissue environments that can, at the same time, be readily transferred across tissue types and species.
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| Web resources: | https://cordis.europa.eu/project/id/101038051 |
| Start date: | 01-06-2021 |
| End date: | 31-05-2023 |
| Total budget - Public funding: | 150 040,32 Euro - 150 040,00 Euro |
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Original description
Application of pulsed electric field (PEF) can reversibly increase the permeability of the cell membrane allowing the access of otherwise impermeable DNA molecules to the inside of the cell. Introduction of foreign DNA molecules encoding immuno-modulatory proteins, antibodies and antigens into cells using PEF, known as Gene Electro-Transfer (GET), is increasingly used for the modulation of the immune system or immunotherapy. While GET based immunotherapy presents itself as a potent application for treatment of cancer and vaccination against infectious diseases, it is suffering from low levels of transgene expressions in vivo. This low efficiency can largely be attributed to our lack of fundamental understanding of the mechanisms by which DNA molecules overcome the barriers of the extra-cellular matrix and the cell membrane in the presence of an electric field. In this action, I aim to provide this required fundamental understanding using principles of polymer physics, soft matter and statistical mechanics. Experiments based on these principles will be conducted in vitro and in vivo to generate results that can be directly compared to theories and models of DNA transport through the extra-cellular matrix and the cell membrane. Understanding the mechanisms within the frameworks of polymer physics will radically improve the efficiency of GET immunotherapy, because it will provide a mechanistic ground for developing optimum protocols within complex tissue environments that can, at the same time, be readily transferred across tissue types and species.Status
CLOSEDCall topic
WF-03-2020Update Date
17-05-2024
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