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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Sweeney P,Karashima T,Ishikura H,Wiehle S,Yamashita M,Benedict WF,Cristiano RJ,Dinney CP

subject

Has Abstract

pub_date

2003-07-15 00:00:00

pages

4017-20

issue

14

eissn

0008-5472

issn

1538-7445

journal_volume

63

pub_type

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