Investigation of using the human polyomavirus, JCV, virus-like particle as a gene delivery vector to inhibit human colon adenocarcinoma growth

博士 === 國立中正大學 === 化學所 === 98 === 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 a...

Full description

Bibliographic Details
Main Authors: Li-Hsien Chen, 陳立賢
Other Authors: Deching Chang
Format: Others
Language:en_US
Published: 2010
Online Access:http://ndltd.ncl.edu.tw/handle/24745639309910505383
Description
Summary:博士 === 國立中正大學 === 化學所 === 98 === 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 gastro-intestinal 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 the current study, a novel in vivo DNA packaging method using the JCV VLP was employed to obtain more highly efficient gene transfer. A reporter gene, the green fluorescence protein (gfp), and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in E. coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intra-peritoneal administration of ganciclovir (GCV) 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.