title: Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.
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.
authors.affiliation: Canji, Inc, San Diego, CA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Connor
authors.forename: H
authors.initials: H
authors.lastname: Engler
authors.forename: T
authors.initials: T
authors.lastname: Machemer
authors.forename: J M
authors.initials: JM
authors.lastname: Philopena
authors.forename: M T
authors.initials: MT
authors.lastname: Horn
authors.forename: S
authors.initials: S
authors.lastname: Sutjipto
authors.forename: D C
authors.initials: DC
authors.lastname: Maneval
authors.forename: S
authors.initials: S
authors.lastname: Youngster
authors.forename: T M
authors.initials: TM
authors.lastname: Chan
authors.forename: J
authors.initials: J
authors.lastname: Bausch
authors.forename: J P
authors.initials: JP
authors.lastname: McAuliffe
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
authors.forename: T L
authors.initials: TL
authors.lastname: Nagabhushan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008297:Male; D009757:Nylons / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D019076:Transgenes / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*; D019459:Urothelium / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D009757:Nylons