Perrie, Yvonne; (1999) Liposomes as a Gene Delivery System. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Several non-viral gene delivery systems are currently being investigated, including liposomes. The present studies attempt to characterise and assess the applicability of liposomes as DNA delivery systems in gene therapy and genetic immunisation. The dehydration-rehydration technique was used to entrap plasmid DNA into liposomes (dehydration-rehydration vesicles; DRV) of varying compositions. Using this procedure, it was shown that plasmid DNA can be efficiently entrapped in DRV in the absence of any detrimental effect on the DNA. The use of cationic lipids as components of liposomes was beneficial but not essential, with vesicles devoid of cationic lipids or incorporating anionic lipids instead, exhibiting significant DNA entrapment values. Entrapped DNA was resistant to nuclease degradation to an extent which was dependent on the DRV lipid composition. The zeta potential and the z-average diameter of DRV vesicles was also dependent on the lipid composition of DRV and, in the case of cationic DRV, on the ratio of cationic lipid to anionic DNA. Microelectrophoresis studies of cationic DRV revealed DNA entrapment in- between of the DNA to the surface of DRV. Although systemic delivery of DNA-containing DRV did not produce detectable gene expression, the formulation employed was shown to offer significant protection to the incorporated plasmid DNA in the presence of plasma at 37°C. In terms of the ability of DNA-containing DRV to induce immune responses to antigens encoded by the DNA, results indicated that DRV with entrapped DNA induce IgG antibody responses against the antigens that are significantly higher than those of equivalent amounts obtained with naked DNA and that variations in the vesicle lipid composition influence the magnitude of such responses. These results suggest that DRV liposomes can act as a vehicle for the delivery of gene vaccines in genetic immunization.

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