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Gene Electro-Transfer Through the Lens of Polymer Physics

Project description

DNA transport based on polymer physics to improve gene electrotransfer efficiency

Introduction of DNA molecules to cells is carried out using pulsed electric fields that increase the permeability of the plasma membrane to DNA. However, the approach still suffers from low levels of gene expression. To address this limitation, the EU-funded GETPolPhys project will combine experiments with existing DNA transport models based on polymer physics to decipher the mechanisms by which the electric field causes DNA molecules to overcome the barriers of the extra-cellular matrix and the cell membrane. The generated knowledge will help improve DNA electrotransfer protocols for applications such as gene therapy, immunotherapy and vaccination against infectious diseases.

Objective

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.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-WF-2018-2020

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Coordinator

UNIVERZA V LJUBLJANI
Net EU contribution
€ 150 040,32
Address
KONGRESNI TRG 12
1000 Ljubljana
Slovenia
Region
Slovenija Zahodna Slovenija Osrednjeslovenska
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 150 040,32