Efficient therapeutic gene delivery after systemic administration of a novel polyethylenimine/DNA vector in an orthotopic bladder cancer model.
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.
Sweeney
Paul
P
Department of Urology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Karashima
Takashi
T
Ishikura
Hisashi
H
Wiehle
Sandy
S
Yamashita
Motoyuki
M
Benedict
William F
WF
Cristiano
Richard J
RJ
Dinney
Colin P N
CP
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
D011094:Polyethyleneimine; D004247:DNA