The successful application of gene therapy is strongly dependent on the ability to transfer therapeutic genes into target cells. Therefore, research in gene therapy has been focused on the development of suitable carriers that would also mediate efficiency intracellular delivery of genetic material. The most efficient method for transferring DNA into cells is the use of viral vectors. However, there are growing concerns about both the short- and long-term risks of viral vectors, the key problems being the immune response they provoke, which can be lethal, the limit on the size of the DNA that can be introduced, and the difficulty and risk of large-scale production of viruses. Hence there have been great efforts to develop a range of non-viral vectors for gene therapy applications and more generally gene deliveries. A broad range of non-viral delivery systems have been described to date, including microinjection, electroporation, and chemical based systems such as calcium phosphate, DEAE-dextran and cationic lipid mediated transfection. Of all the non-viral vectors, cationic lipids have shown the most promise for in vivo applications, based on a combination of efficiency, stability and lack of toxicity. Since the first application of cationic lipids in DNA delivery, numerous cationic lipids have been synthesised, and some of these have been used in gene therapy clinical trials while many others have become established as the most common method for the transfection of a varies of cell lines in vitro.

The presence of so many steps in the transfection pathway means that it has been very difficult to generate strong structure-activity relationships for transfection compounds. Combinatorial solid-phase synthesis allows highly efficient production and purification of diverse libraries of compounds in the search for new therapeutic agents. The aim of this project is the synthesis of transfection agents using combinatorial chemistry and the structure-transfection activity relationships studies of these compounds in vitro.