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

Objectives. Replication deficient adenoviral vectors (rAds) are used as gen e delivery systems that can efficiently transduce a variety of tissues and may be appropriate vectors to develop gene therapeutics for many urologic a pplications. However, the bladder epithelium has been shown to be highly re sistant to transgene expression after intracystic administration. A potenti al 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 enh ance adenovirus-mediated transgene expression. Methods. Normal and bladder tumor-bearing rats received a single intracysti c administration of rAd encoding beta-galactosidase (rAd-beta gal) or p53 ( rAd-p53), rAd was administered in a saline solution or in solutions with in creasing concentrations of ethanol, Transgene expression was evaluated in t he bladder tissues. Results. A dramatic increase in urothelial beta-galactosidase transgene exp ression was achieved by rAd-beta gal 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 t ransgene expression in the normal and neoplastic bladder epithelium in rode nts. Improvement of rAd-mediated transgene expression is progress toward lo cal gene delivery to the urothelium and may enable local gene therapy for s uperficial bladder cancer or other bladder diseases. UROLOGY 53: 1049-1053, 1999. (C) 1999, Elsevier Science Inc. All rights reserved.