title: Polymer-enhanced delivery increases adenoviral gene expression in an orthotopic model of bladder cancer.
abstract: Gene therapy has garnered significant attention as a therapeutic approach for bladder cancer but efficient delivery and gene expression remain major hurdles. The goal of this study was to determine if cationic polymers can enhance adenoviral gene expression in cells that are difficult to transduce in vitro and to subsequently investigate lead candidates for their capacity to increase adenoviral gene expression in an orthotopic in vivo model of bladder cancer. In vitro screening of linear polyamine-based and aminoglycoside-based polymer libraries identified several candidates that enhanced adenoviral reporter gene expression in vitro. The polyamine-based polymer NPGDE-1,4 Bis significantly enhanced adenoviral gene expression in the orthotopic model of bladder cancer but unfortunately further use of this polymer was limited by toxicity. In contrast, the aminoglycoside-based polymer paromomycin-BGDE, enhanced adenoviral gene expression within the bladder without adverse events. Our study demonstrates for the first time that cationic polymers can enhance adenoviral gene expression in an orthotopic model of bladder cancer, thereby providing the foundation for future studies to determine therapeutic benefits of polymer-adenovirus combination in bladder cancer gene therapy.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Gosnell
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Kasman
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe 85287-6106 USA.
authors.forename: Thrimoorthy
authors.initials: T
authors.lastname: Potta
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe 85287-6106 USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Vu
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe 85287-6106 USA.
authors.forename: Kaushal
authors.initials: K
authors.lastname: Rege
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425, USA. Electronic address: johnsocv@musc.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: Voelkel-Johnson
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D015870:Gene Expression; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D011108:Polymers; D049452:Green Fluorescent Proteins; D008156:Luciferases
keywords: Adenovirus; Bladder cancer; Cationic polymer; Gene delivery; Orthotopic