Durable Expression of Minicircle DNA-Liposome-Delivered Androgen Receptor cDNA in Mice with Hepatocellular Carcinoma

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 sa...

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Bibliographic Details
Published in:BioMed research international 2014-01, Vol.2014 (2014), p.1-9
Main Authors: Chuang, Wei-Min, Chang, Tian-You, Ma, Wen-Lung, Jeng, Long-Bin, Li, Long-Yuan, Chung, Chin-Ying
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Hepatocellular - metabolism
Cations
Deoxyribonucleic acid
DNA
DNA, Complementary - chemistry
Gene Expression Regulation, Neoplastic
Gene Transfer Techniques
Genetic Therapy - methods
Green Fluorescent Proteins - chemistry
Immune system
Lipids
Lipids - chemistry
Liposomes - chemistry
Liver - metabolism
Liver cancer
Liver Neoplasms - metabolism
Luciferases - chemistry
Medical research
Medicine
Metastasis
Mice
Mice, Transgenic
Neoplasm Metastasis
Permeability
Plasmids
Protein expression
Proteins
Receptors, Androgen - metabolism
Retention
Tumors
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Summary: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. Conclusion. Our results show that an MC/liposome delivery system might improve the efficacy of gene therapy in patients with HCC.
ISSN:2314-6133
2314-6141
DOI:10.1155/2014/156356