Ethanol improves adenovirus-mediated gene transfer and expression to the bladder epithelium of rodents

Abstract

Objectives. Replication deficient adenoviral vectors (rAds) are used as gene delivery systems that can efficiently transduce a variety of tissues and may be appropriate vectors to develop gene therapeutics for many urologic applications. However, the bladder epithelium has been shown to be highly resistant to transgene expression after intracystic administration. A potential explanation for this low gene transfer efficiency may be the protective structure of the urothelium. Since this protective barrier can be disrupted by organic solvents, we assessed whether ethanol co-administration can enhance adenovirus-mediated transgene expression.Methods. Normal and bladder tumor-bearing rats received a single intracystic administration of rAd encoding β-galactosidase (rAd-βgal) or p53 (rAd-p53). rAd was administered in a saline solution or in solutions with increasing concentrations of ethanol. Transgene expression was evaluated in the bladder tissues.Results. A dramatic increase in urothelial β-galactosidase transgene expression was achieved by rAd-βgal administered in a 22% ethanol solution. Transgene expression was enhanced in normal urothelium and in superficial bladder tumors. p53 transgene expression was similarly enhanced.Conclusions. Co-administration of 22% ethanol enhanced local rAd-mediated transgene expression in the normal and neoplastic bladder epithelium in rodents. Improvement of rAd-mediated transgene expression is progress toward local gene delivery to the urothelium and may enable local gene therapy for superficial bladder cancer or other bladder diseases.