1. Efficient therapeutic gene delivery after systemic administration of a novel polyethylenimine/DNA vector in an orthotopic bladder cancer model.
- Author
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Sweeney P, Karashima T, Ishikura H, Wiehle S, Yamashita M, Benedict WF, Cristiano RJ, and Dinney CP
- Subjects
- Animals, DNA genetics, Genes, p53, Genetic Vectors adverse effects, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Polyethyleneimine adverse effects, Transduction, Genetic, Urinary Bladder Neoplasms genetics, Xenograft Model Antitumor Assays, DNA administration & dosage, Genetic Therapy methods, Genetic Vectors administration & dosage, Polyethyleneimine administration & dosage, Urinary Bladder Neoplasms therapy
- 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.
- Published
- 2003