Liver-specific expression of an exogenous gene controlled by human apolipoprotein A-I promoter.

【作者】 Yurong Hu, Xueling Ren,Hui Wang,Yue Ma,Lei Wang,Yingying Shen,Oka. Kazuhiro,Zhenzhong Zhang*,Yun Zhang

【期刊名】International Journal of Pharmaceutics

【影响因子】 2010年:3.607

【作者单位】 Zhengzhou Univ, Sch Pharm, 100 Sci Rd, Zhengzhou 450001, Henan, Peoples R China.

【年，卷(期)：页码】2010.10.15,398(1-2):161-164

【关键词】Liver-specificexpression; Hepatocellular carcinoma; Pegylated immuno-lipopolyplexes; Gene therapy; Promoter; ApolipoproteinA-I

【摘要】Liver-specificgene therapy is advantageous to minimize the possible adverse effects caused by nontarget geneexpression. The CMV promoterof the enhanced green fluorescent protein (EGFP) expressing plasmid pCMV-EGFP was replaced with the liver-specificpromoterapolipoproteinA-I (ApoAI) generating pApoAI-EGFP plasmid. In vitro expression experiments performed in various cell lines including HepG2, SMMC-7721, MCF7, ACC-2 and Lo2 indicated that pCMV-EGFP treatment caused geneexpression in all the cell lines, whereas pApoAI-EGFP treatment only induced EGFP expression in cells of liver origin including the liver cancer cells HepG2 and SMMC-7721 and the normal liver cells Lo2. Either pCMV-EGFP or pApoAI-EGFP was formulated as pegylated immuno-lipopolyplexes (PILP), a novel and efficient gene delivery system. Following intravenous administration of the PILP in H22 tumor-bearing mice, there was significant EGFP expression in liver, tumor, spleen, brain and lung in the pCMV-EGFP treated mice, whereas in the pApoAI-EGFP treated mice there was only geneexpression in liver and tumor and the non-liver organ geneexpression was eliminated. This study suggests that the use of the PILP technology and liver-specificpromoter enables efficient and liver-specificexpressionofanexogenousgene. (C) 2010 Elsevier B.V. All rights reserved

【全文链接】http://www.sciencedirect.com/science/article/pii/S037851731000550