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Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model

Gene Therapy volume 17, pages 1033–1041 (2010)Cite this article

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Abstract

The JC virus (JCV) may infect human oligodendrocytes and consequently cause progressive multifocal leukoencephalopathy (PML) in patients with immune deficiency. In addition, the virus has also been detected in other human tissues, including kidney, B lymphocytes, and gastrointestinal tissue. The recombinant major structural protein, VP1, of JCV is able to self-assemble to form a virus-like particle (VLP). It has been shown that the VLP is capable of packaging and delivering exogenous DNA into human cells for gene expression. However, gene transfer is not efficient when using in vitro DNA packaging methods with VLPs. In this study, a novel in vivo DNA packaging method using the JCV VLP was used to obtain high efficiency gene transfer. A reporter gene, the green fluorescence protein, and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in Escherichia coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intraperitoneal administration of ganciclovir in the tk-VLP-treated mice greatly reduced tumor volume. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human colon cancer therapy in the future.

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Acknowledgements

This work was supported by the National Science Council grant NSC97-2320-B-194-001-MY3, Taiwan and Chang Gung Memorial Hospital at Chia-Yi, Chang Gung University grant CMRPG680181, Taiwan.

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Authors and Affiliations

  1. Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, ROC

    L-S Chen, C-Y Fung, C-F Chang & D Chang

  2. Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi, Taiwan, ROC

    L-S Chen

  3. Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC

    M Wang

  4. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC

    W-C Ou & P-L Chen

  5. Department of Colorectal Surgery, Chang Gung Memorial Hospital at Chia-Yi, Chang Gung University, Chia-Yi, Taiwan, ROC

    W-S Huang & J-Y Wang

  6. Department of Pathology, Chang Gung Memorial Hospital at Chia-Yi, Chang Gung University, Chia-Yi, Taiwan, ROC

    P Y Lin

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  1. L-S Chen
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Correspondence to P Y Lin or D Chang.

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Chen, LS., Wang, M., Ou, WC. et al. Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model. Gene Ther 17, 1033–1041 (2010). https://doi.org/10.1038/gt.2010.50

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