Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium

Adenovirus-mediated gene therapy of bladder diseases has been limited by th e inability to transduce the urothelium successfully using adenoviral vecto rs. We have sought to identify agents that would increase adenovirus-mediat ed transgene expression in the bladder. We have utilized a rat model to scr een compounds for their ability to enhance viral transgene expression in th e rat bladder. Rats received intravesical administration of replication-def icient adenovirus (rAd) formulated in various agents, and transgene express ion was evaluated after 48 h by determining the amount of lacZ expression i n the luminal epithelium of the bladder. We report the identification of tw o different polyamides, each capable of dramatically increasing viral trans gene expression in the bladder without causing detectable alteration of the umbrella cell layer of the urothelium. We have utilized a carcinogen-induc ed rat bladder tumor model to demonstrate that these polyamides are also ca pable of enhancing viral transgene expression in tumor tissue. The identifi cation of these polyamides potentiates the use of adenovirus-mediated gene therapy for the treatment of superficial bladder cancer or other bladder di seases.