AIDS THERAPY VIA LIPOSOME-MEDIATED GENE DELIVERY

最近的研究表明，基因治疗对于癌症是可行的。 艾滋病的治疗。人类免疫缺陷病毒调控白喉基因的表达 A毒素片段(IV-DTA)对HIV感染的抵抗力 人类细胞系。基因治疗的主要问题之一是 有效地将治疗性基因导入靶细胞。这 该项目将探索和建立传递HIV-DTA结构的方法， 可从Project 1获得，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质粒传递给单核细胞和 淋巴细胞株、外周血单核细胞和 巨噬细胞将被建立。将确定艾滋病毒是否- DTA载体脂质体在体内长时间循环的研究 血液蒸汽和具有渗入组织的能力，可以 输送到巨噬细胞中。HIV-DTA质粒是否包裹了 在pH敏感的脂质体中可以有效地输送到 将测定单核/巨噬细胞。的保护作用。 在细胞系和细胞中传递抗新生HIV-1感染的HIV-DTA 原代细胞将被评估，并且表达的稳定性 基因将被确定。这些研究将构成 脂质体介导的HIV-DTA载体进入细胞内的实验研究 9001项目中的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.