Farhood H, Gao X, Son K, Yang Y Y, Lazo J S, Huang L, Barsoum J, Bottega R, Epand R M
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Ann N Y Acad Sci. 1994 May 31;716:23-34; discussion 34-5. doi: 10.1111/j.1749-6632.1994.tb21701.x.
Cationic liposomes can mediate efficient delivery of DNA and DNA/protein complex to mammalian cells in vitro and in vivo. Cationic cholesterol derivatives mixed with phosphatidylethanolamine and sonicated to form small unilamellar vesicles can complex with DNA and mediate the entry into the cytosol from the endosome compartment. One of the liposome formulations, DC-Chol liposomes, is used in a gene therapy clinical trial for melanoma. Recently, we exploited these cationic liposomes for the delivery of trans-activating protein factors to regulate and control the expression of delivered transgenes in a protein dose-dependent manner. Bacteriophage T7 RNA polymerase was co-delivered with a reporter gene under the control of T7 promoter to allow cytoplasmic expression of the gene. Human immunodeficiency virus-1 transactivating protein was also codelivered with a reporter gene under the control of HIV-1 long terminal repeat. Finally, human tumor cells selected for cis-platin resistance or isolated from patients who have failed cis-platin therapy are highly transfectable with cationic liposomes. These results suggest a serial therapy protocol with cis-platin and gene therapy for malignancy.
阳离子脂质体能够在体外和体内将DNA以及DNA/蛋白质复合物高效递送至哺乳动物细胞。将阳离子胆固醇衍生物与磷脂酰乙醇胺混合并超声处理以形成小单层囊泡，其可与DNA复合并介导从内体区室进入细胞质。脂质体制剂之一，即DC-Chol脂质体，被用于一项针对黑色素瘤的基因治疗临床试验。最近，我们利用这些阳离子脂质体来递送反式激活蛋白因子，从而以蛋白质剂量依赖性方式调节和控制所递送转基因的表达。噬菌体T7 RNA聚合酶与一个受T7启动子控制的报告基因共同递送，以使该基因在细胞质中表达。人类免疫缺陷病毒1反式激活蛋白也与一个受HIV-1长末端重复序列控制的报告基因共同递送。最后，选择的对顺铂耐药的人类肿瘤细胞或从顺铂治疗失败的患者中分离出的肿瘤细胞，对阳离子脂质体具有高度转染性。这些结果提示了一种针对恶性肿瘤的顺铂与基因治疗联合疗法方案。
