Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model.
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.
Chen
L-S
LS
Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, ROC.
Wang
M
M
Ou
W-C
WC
Fung
C-Y
CY
Chen
P-L
PL
Chang
C-F
CF
Huang
W-S
WS
Wang
J-Y
JY
Lin
P Y
PY
Chang
D
D
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D004926:Escherichia coli / Q000235:genetics; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D007577:JC Virus / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014771:Virion / Q000235:genetics
D049452:Green Fluorescent Proteins; D015774:Ganciclovir