Liposome mediated gene transfer.
ABSTRACT Liposomes, artificial membrane vesicles, are being intensively studied for their usefulness as delivery vehicles in vitro and in vivo. Substantial progress has been made in the development of procedures for liposome preparation, targeting and delivery of contents. The broad flexibility now available in the design of the structure and composition of liposomes, coupled to recent reports of liposome mediated gene transfer in animals, suggest that liposome technology is now poised to be utilized in the creation of custom-designed cell-type-specific gene transfer vehicles.
- SourceAvailable from: epub.ub.uni-muenchen.deAnnals of the New York Academy of Sciences 12/2006; 716(1):36 - 58. · 4.38 Impact Factor
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ABSTRACT: Elucidation of the many roles of nitric oxide (NO) in homeostasis and disease states has uncovered many areas where manipulation of NO production would be of therapeutic benefit. Recent advances in gene transfer technology and the cloning of the inducible nitric oxide synthase (iNOS) gene have led to the development of strategies for gene therapy to increase NO production for the treatment of disorders ranging from vascular restenosis to impaired wound healing. This review summarizes the current status of iNOS gene therapy research.World Journal of Surgery 08/2002; 26(7):772-8. · 2.23 Impact Factor
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ABSTRACT: Liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines, possibly by facilitating uptake of the plasmid by antigen-presenting cells (APC). In this paper, we have investigated the influence of the liposomal composition and surface charge on such potency. Plasmid DNA pRc/CMV HBS encoding the S (small) region of hepatitis B surface antigen was entrapped within cationic liposomes of various compositions and surface charges with high efficiency (88-97% of the amount used) by the dehydration-rehydration method that generates dehydration-rehydration vesicles (DRV). Cryo-electron microscopy revealed that DNA-containing DRV (DRV(DNA)) were multilamellar. In immunisation studies, female Balb/c mice were given two to four intramuscular injections of 10 microg naked or liposome-entrapped pRc/CMV HBS and bled at time intervals. Results indicate that the lipid composition of the DRV(DNA) influences the strength of the humoural response (immunoglobulin (Ig)G subclasses) with inclusion of dioleoyl phosphatidylethanolamine (DOPE) or phosphatidylethanolamine (PE) in the liposomal structure contributing to greater responses. DRV(DNA) in which the DOPE or PE were omitted or substituted with cholesterol led to significant reduction of humoural responses against the encoded antigen. Replacing phosphatidylcholine (PC) in the DRV(DNA) with the high-melting distearoyl phosphatidylcholine also contributed to lower responses. In other experiments, IgG responses were monitored in mice immunised with pRc/CMV HBS entrapped in DRV composed of PC and DOPE as before but incorporating increasing amounts of DOTAP (1-16 micromol). Maximal IgG responses were observed at 10 weeks after the first of four injections and suggested a trend of higher responses when 4 or 8 micromol DOTAP was present in the DRV(DNA) formulation. Cell-mediated immunity (measured in terms of endogenous antigen-specific splenic interferon-gamma) in mice immunised with pRc/CMV HBS entrapped in liposomes composed of PC, DOPE and DOTAP (16:8:4 molar ratio) was much greater than in animals treated with naked plasmid. These results indicate that liposome-mediated DNA immunisation is more effective than the use of naked DNA, and also suggest that the presence of fusogenic phosphatidylethanolamine in DRV in conjunction with a low-melting phosphatidylcholine and an appropriate content of cationic lipid might contribute to more effective liposomal DNA vaccines. The notion that liposomes improve immune responses to the plasmid-encoded vaccine by facilitating the latter's uptake by APC was supported by the observation that in Balb/c mice injected intramuscularly with liposome-entrapped pCMV. Enhanced green fluorescent protein, expression of the gene in terms of fluorescence intensity in the draining lymph nodes, was much greater than in animals treated with the naked plasmid.Vaccine 05/2001; 19(23-24):3301-10. · 3.49 Impact Factor