Use this URL to cite or link to this record in EThOS:
Title: Development of cationic lipids for gene delivery systems
Author: Wong, John Bosco Chun-Chung
ISNI:       0000 0001 3571 5127
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2006
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available