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EPSRC Reference: GR/S05878/01
Title: Chemical and Macromolecular Structure of lipids for gene therapy: A Synthetic and Biophysical Study
Principal Investigator: Hailes, Professor HC
Other Investigators:
Tabor, Professor A Hart, Professor SL Ayazi Shamlou, Professor P
Levy, Dr MS Lawrence, Professor MJ
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: UCL
Scheme: Standard Research (Pre-FEC)
Starts: 01 September 2003 Ends: 31 August 2006 Value (£): 83,435
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Drug Formulation & Delivery
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Recently it was reported that a non-viral vector consisting of a cationic lipid, a peptide with cationic and receptor targeting motifs, and plasmid DNA ad high transfection efficiency in vitro and low toxicity. These components assemble electrostatistically in solution to form vector particles. Peptide and lipids are convenient vector components that can be synthesised, purified and combined in different ratios, enabling the production of a well characterised vector formulation. The first generation lipid/peptide/DNA vector consisted of integrin-targeting peptides and Lipofectin (DOTMA:DOPE, 1:1) where the cationic lipid component enhances transfection by endosomal disruption. The proposed research is a novel, systematic approach to understanding, at a structural level, the important structural parameters for successful non-viral gene delivery.We aim to explore the relationship between lipid structure, aggregation properties, transfection efficiency of the resulting LID vector and mode of action of the vector by : developing new methodology for the synthesis of novel lipids and lipopeptides; synthesising a range of lipids and lipopeptides, designed to test a number of hypotheses about the optimal structures for maximum transfection efficiency, and test the transfection efficiencies of the resulting vectors in vitro, and of selected vectors in vivo. Furthermore, we will assess the physicochemical properties of the LID vector and its components and test the transfection pathway via confocal microscopy.
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