Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model
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Published on: March 22, 2011
1Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, ROC.
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.
Insights
This study developed a novel in vivo method using JC virus-like particles (VLPs) for efficient gene delivery. The JC virus VLP successfully targeted colon cancer cells in mice, significantly reducing tumor volume when combined with a suicide gene therapy.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- JC virus (JCV) infects oligodendrocytes, causing progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals.
- JCV has been detected in various human tissues, including kidney, B lymphocytes, and gastrointestinal tissue.
- JCV major structural protein (VP1) self-assembles into virus-like particles (VLPs) capable of DNA packaging and delivery.
Purpose of the Study:
- To develop a novel in vivo DNA packaging method using JCV VLPs for high-efficiency gene transfer.
- To evaluate the potential of JCV VLPs as a gene delivery vector for colon cancer therapy.
Main Methods:
- Encapsidation of reporter (green fluorescence protein) and suicide (herpes simplex virus thymidine kinase) genes into JCV VLPs in E. coli.
- In vivo targeting of human colon carcinoma cells (COLO-320 HSR) in a nude mouse model using engineered VLPs.
- Administration of ganciclovir to mice treated with tk-VLP for tumor reduction assessment.
Main Results:
- The novel in vivo method achieved high efficiency gene transfer using JCV VLPs.
- JC virus VLPs specifically targeted human colon carcinoma cells in a nude mouse model.
- Intraperitoneal ganciclovir administration in tk-VLP-treated mice resulted in significant tumor volume reduction.
Conclusions:
- JC virus VLPs can be effectively engineered for in vivo gene delivery.
- The developed method shows promise for targeted gene therapy in colon cancer.
- JCV VLPs represent a potential future gene delivery vector for human colon cancer treatment.
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