Liver-specific expression of an exogenous gene controlled by human apolipoprotein A-I promoter.
Liver-specific gene therapy is advantageous to minimize the possible adverse effects caused by non-target gene expression. The CMV promoter of the enhanced green fluorescent protein (EGFP) expressing plasmid pCMV-EGFP was replaced with the liver-specific promoter apolipoprotein A-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 gene expression 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 gene expression in liver and tumor and the non-liver organ gene expression was eliminated. This study suggests that the use of the PILP technology and liver-specific promoter enables efficient and liver-specific expression of an exogenous gene.
Hu
Yurong
Y
School of Pharmacy, Zhengzhou University, Zhengzhou 450001, Henan, PR China.
Ren
Xueling
X
Wang
Hui
H
Ma
Yue
Y
Wang
Lei
L
Shen
Yingying
Y
Oka
Kazuhiro
K
Zhang
Zhenzhong
Z
Zhang
Yun
Y
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000502:physiology*
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I