Wong, JBC-C;
(2006)
Development of cationic lipids for gene delivery systems.
Doctoral thesis , UCL (University College London).
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Abstract
This thesis describes investigations into the structural requirements of cationic lipids leading to optimal formulations in a non-viral, ternary lipid/peptide/DNA (LID) delivery system. Initially, the principles behind current strategies of gene therapy are described. A literature review of the synthesis and effectiveness of cationic lipids used for gene therapy is presented. The principles of utilising antibody fragments and integrins for receptor-mediated gene delivery are also described. The lipid/peptide/DNA vector system is introduced and the advantages it possesses are outlined. The results and discussion starts in Chapter 2, which outlines the synthetic procedures to generate DOTMA lipid analogues. The results of a systematic investigation into the lipid component in the LID vector formulations are presented and discussed. The influence of lipid structural features on the LID transfection efficiencies and the liposome stabilities are outlined. The synthesis of fluorescently- labelled lipids is also described. The synthesis and biological activity of lipid analogues bearing short polyethylene glycol (PEG) chains are given in Chapter 3. The development of a novel class pH-sensitive PEG lipids is outlined in Chapter 4, and the lipid stabilities over a pH range as well as its influence on transfection efficiencies is presented and discussed. Synthetic routes to dicationic lipid analogues bearing erythritol and pentaerythritol backbone are presented in Chapter 5, where several strategies are considered. In Chapter 6 synthetic routes toward lipopeptides and immunoliposomes for receptor-mediated gene delivery are outlined. An overall summary and possible areas of research in future are discussed in Chapter 7. A formal description of the experimental methods and procedures is presented in Chapter 8.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Development of cationic lipids for gene delivery systems |
| Identifier: | PQ ETD:593316 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1445990 |
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