Bladder cancer is one of the most common cancers of the urinary tract. The poor 5-year survival rate of invasive bladder cancer presents a challenge for bladder cancer treatment. Previous studies have demonstrated that human urothelial carcinomas are susceptible to infection by the JC polyomavirus (JCPy). In this study, JCPy virus-like particles (VLPs) were employed to deliver genes into human urothelial carcinoma cells for possible therapeutic investigation.

Reporter plasmids, pEGFP-N3, for expressing green fluorescent protein (GFP), LacZ expression plasmids bearing CMV or mucin 1 (Muc1) promoter, and a functional plasmid, pUMVC1-tk, for expressing thymidine kinase (TK) were packaged into JCPy VLPs. The plasmid DNAs were transduced via the JCPy VLPs into human urothelial carcinoma cells in vitro and into xenografted human bladder tumor nodules in vivo.

The results show that the pEGFP-N3 DNA was delivered and GFP was expressed in both the human urothelial carcinoma cells in vitro and the tumor nodules of mice in vivo; the TK transgene was also functioning both in vitro and in vivo after JCPy VLP transduction. Moreover, the size of the TK gene-transduced urothelial carcinoma nodules was drastically reduced in the presence of acyclovir. In addition, selective Muc1-LacZ expression in human urothelial carcinoma cells transduced by JCPy VLPs was demonstrated.

These findings provide a possible approach for human urothelial carcinoma gene therapy by using JCPy VLPs in the future.