title: Durable expression of minicircle DNA-liposome-delivered androgen receptor cDNA in mice with hepatocellular carcinoma.
abstract: BACKGROUND
  The most common gene-based cancer therapies involve the suppression of oncogenic molecules and enhancement of the expression of tumor-suppressor genes. Studies in noncancer disease animal models have shown that minicircle (MC) DNA vectors are easy to deliver and that the proteins from said MC-carrying DNA vectors are expressed over a long period of time. However, delivery of therapeutic genes via a liposome-mediated, MC DNA complex has never been tested in vascular-rich hepatocellular carcinoma (HCC). Liposome-mediated DNA delivery exhibits high in vivo transfection efficiency and minimal systemic immune response, thereby allowing for repetitive interventions. In this study, we evaluated the efficacy of delivering an MC-liposome vector containing a 3.2 kb androgen receptor (AR; HCC metastasis suppressor) cDNA into Hepatitis B Virus- (HBV-) induced HCC mouse livers.
  
  
  RESULTS
  Protein expression and promoter luciferase assays revealed that liposome-encapsulated MC-AR resulted in abundant functional expression of AR protein (100 kD) for up to two weeks. The AR cDNA was also successfully delivered into normal livers and diseased livers, where it was persistently expressed. In both normal livers and livers with tumors, the expression of AR was detectable for up to 60 days.
  
  
  CONCLUSIONS
  Our results show that an MC/liposome delivery system might improve the efficacy of gene therapy in patients with HCC.
authors.affiliation: Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan ; Graduate Institution of Clinical Medical Science, Department of Medicine, School of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Tian-You
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Chin-Ying
authors.initials: CY
authors.lastname: Chung
authors.affiliation: Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan ; Graduate Institution of Clinical Medical Science, Department of Medicine, School of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chuang
authors.affiliation: Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
authors.affiliation: Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.affiliation: Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan ; Graduate Institution of Clinical Medical Science, Department of Medicine, School of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Wen-Lung
authors.identifier: 0000-0002-5571-3302
authors.initials: WL
authors.lastname: Ma
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002412:Cations; D018076:DNA, Complementary / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008156:Luciferases / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D002412:Cations; D018076:DNA, Complementary; D008055:Lipids; D008081:Liposomes; D011944:Receptors, Androgen; D049452:Green Fluorescent Proteins; D008156:Luciferases
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