Abstract:
:Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for their ability to enhance viral transgene expression in the rat bladder. Rats received intravesical administration of replication-deficient adenovirus (rAd) formulated in various agents, and transgene expression was evaluated after 48 h by determining the amount of lacZ expression in the luminal epithelium of the bladder. We report the identification of two different polyamides, each capable of dramatically increasing viral transgene expression in the bladder without causing detectable alteration of the umbrella cell layer of the urothelium. We have utilized a carcinogen-induced rat bladder tumor model to demonstrate that these polyamides are also capable of enhancing viral transgene expression in tumor tissue. The identification of these polyamides potentiates the use of adenovirus-mediated gene therapy for the treatment of superficial bladder cancer or other bladder diseases.
journal_name
Gene Therjournal_title
Gene therapyauthors
Connor RJ,Engler H,Machemer T,Philopena JM,Horn MT,Sutjipto S,Maneval DC,Youngster S,Chan TM,Bausch J,McAuliffe JP,Hindsgaul O,Nagabhushan TLdoi
10.1038/sj.gt.3301348keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
41-8issue
1eissn
0969-7128issn
1476-5462journal_volume
8pub_type
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