Research objectives and content
Cationic liposomes complexed with DNA are among the most promising non viral carrier vectors for gene therapy. Recent investigations by Radler reveal a novel multilamellar structure of cationic lipid/DNA complexes with alternating lipid bilayers and DNA monolayers.
The aim of this project is to design similar arrangements by the Langmuir-Blodgett (LB) method and to investigate their nanostructure by complementary techniques: neutrons scattering, synchroton X-ray diffraction, electron and optical microscopy. Systematic studies of physicochemical parameters would give insights into the driving forces of the formation of the gene vectors and would contribute to improve gene therapy efficiency.
In this project, our proposal consists in: i) continuing the recent investigations of lipid/DNA and lipid/DNA/polypeptide gene transfer complexes in collaboration with the medical group of Moradpour and Blum (Freiburg, Germany). The transfection efficiency will be related to their molecular structure. ii) investigation of interaction forces and basic molecular self-assembly principles in lipid/DNA complexes using oriented liquid crystalline probes in LB films.
Training content (objective, benefit and expected impact)
- Various and complementary techniques will be used for this study - In the laboratory: specialised optical microsocopy, DSC, electron microsocopy, ... - In different places in Europe: synchrotron X-rays and neutrons scattering experiments - New samples will be prepared by the Langmuir-Blodgett techniques. - A structural approach of the DNA/Cationic lipids complexes will get insight into the driving forces of complexes formations, and their stability during gene transfection therapy. Links with industry / industrial relevance (22)
This work have relevance to the promising non-viral gene therapy. All pharmaceutical groups are interesting, and develop extensively this new strategy of therapy. J. Rddler collaborates with Hoechst and Biotuls.