AIDS THERAPY VIA LIPOSOME-MEDIATED GENE DELIVERY

最近的研究表明，基因治疗的可行性， 治疗艾滋病。 HIV调节白喉基因的表达 毒素A片段（IV-DTA）赋予抗HIV感染的抗性， 人类细胞系。 基因治疗的主要问题之一是 将治疗性基因有效递送到靶细胞中。 这 该项目将探索和建立提供HIV-DTA结构的方法， 可从项目1获得的脂质体，进入各种细胞，使用脂质体作为 载体和转染剂。 最有效的阳离子脂质体 用于将HIV-DAT质粒递送至单核细胞和 淋巴细胞系和外周血单核细胞， 将建立巨噬细胞。 将确定艾滋病毒- 包封在脂质体中的DTA质粒在体内循环时间延长 血液蒸汽并具有外渗到组织中的能力， 进入巨噬细胞。 HIV-DTA质粒是否包裹 在pH敏感性脂质体中， 将测定单核细胞/巨噬细胞。 的保护作用 在细胞系中递送抗从头HIV-1感染的HIV-DTA， 将评价原代细胞，并测定表达的稳定性。 基因将被确定。 这些研究将为 脂质体介导的HIV-DTA构建体向细胞中的递送， 项目9001中的SCID-Hu小鼠模型。

Recent studies have shown the feasibility of gene therapy for the treatment of AIDS. HIV regulated expression of the gene for Diphtheria toxin A fragment (IV-DTA) confers resistance against HIV infection in human cell lines. One of the major problems of gene therapy is the effective delivery of the therapeutic gene into target cells. This project will explore and establish means to deliver HIV-DTA constructs, available from Project 1, into a variety of cells, using liposomes as carriers and transfection agents. The most effective cationic liposome composition for the delivery of HIV-DAT plasmids to monocytic and lymphocytic cell lines, and peripheral blood mononuclear cells and macrophages will be established. It will be determined whether the HIV- DTA plasmid encapsulated in liposomes with prolonged circulation in the blood steam and with the ability to extravasate into tissues, can be delivered into macrophages. Whether the HIV-DTA plasmids encapsulated in pH-sensitive liposomes can be delivered effectively to monocyte/macrophages will be determined. The protective effect of the delivered HIV-DTA against de novo HIV-1 infection in cell lines and primary cells will be evaluated, and the stability of expression of the genes will be determined. These studies will constitute a foundation for the liposome-mediated delivery of HIV-DTA constructs into cells in the SCID-Hu mouse model in Project 9001.