嘉義基督教醫院 1外科部 泌尿科 2醫學研究部；3國立中正大學 分子生物研究所; 4中山醫學大學 醫學院 生化微生物免疫研究所
Peptide-guided JCPyV virus like particles specifically target bladder cancer cells
Pin-Jui Huang1, Wei-Hong Lai1, Chiung-Yao Fang2, Mien-Chun Lin1, Cheng-Huang Shen1, Deching Chang3, Meilin Wang4
1Department of Urology; 2Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan; 3Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. 4 Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
Introduction & objectives
The ultimate goal of developing gene delivery vectors is to establish a specific and effective treatment for human diseases. In the current study, we attempt to develop peptide-guided human JC virus (JCPyV) virus-like particles (VLPs) as a gene delivery vector specifically targeting a therapeutic gene to bladder cancer cells for expression. Our previous studies have demonstrated that the JCPyV VLPs are able to package and deliver exogenous DNA into the susceptible cells for gene expression. For tissue specific targeting investigation in this study, the JCPyV VLPs were conjugated with a peptide (SPB) which specifically binds to bladder cancer cells.
Materials & methods:
The suicide gene, thymidine kinase (tk), was packaged and delivered by the SPB tagged VLP (VLP-SPB). Human bladder cancer, lung cancer and neuroblastoma cancer cells susceptible to the JCPyV VLPs infection were employed for targeting specificity tests.
Results show that the VLP-SPB could specifically target bladder cancer cells but not lung cancer and neuroblastoma cells to express the suicide gene. The targeting specificity of the VLP-SPB was demonstrated both in vitro and in vivo. Furthermore, we have also found that gene transduction efficiency of the VLP-SPB is about 100 times more than that of the VLP without tagged with the peptide.
This study demonstrates that the JCPyV VLPs can be guided by a bladder cancer specific binding peptide to target bladder cancer cells with high specificity and efficiency for gene therapy.