title: Efficient therapeutic gene delivery after systemic administration of a novel polyethylenimine/DNA vector in an orthotopic bladder cancer model.
abstract: Successful systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after i.v. administration. To circumvent these problems, we developed a novel formulation between the polycation polyethyleneimine and DNA that mediates high-level tumor cell transduction in vitro and efficient i.v. gene delivery in that greater reporter gene expression occurred in tumor than in lung. Strikingly, administration of just 6 micro g of the polyethyleneimine/DNA-p53 vector every 3 days for 3 weeks indicated restoration of normal cell cycle regulation and apoptotic mechanisms as demonstrated by efficient p53 expression, increased apoptosis, and a 70% reduction in tumor size in an orthotopic bladder cancer model. This novel vector formulation represents a new method to increase i.v. delivery of genes to tumors.
authors.affiliation: Department of Urology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Sweeney
authors.forename: Takashi
authors.initials: T
authors.lastname: Karashima
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishikura
authors.forename: Sandy
authors.initials: S
authors.lastname: Wiehle
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: William F
authors.initials: WF
authors.lastname: Benedict
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cristiano
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000009:adverse effects; D014161:Transduction, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D011094:Polyethyleneimine; D004247:DNA