Similar Efficiency of DNA-Liposome Complexes and Retrovirus-Producing Cells for HSV-tkSuicide Gene Therapy of Peritoneal Carcinomatosis

1 January 2000

journal article
research article
Published by Taylor & Francis in Journal of Drug Targeting

Vol. 8 (2) , 79-89
https://doi.org/10.3109/10611860008996854

Abstract

Several experimental approaches have been tested for suicide gene delivery into tumor cells, including viral and non-viral vectors. In this study, we compared the efficiency of Herpes Simplex Virus type 1 thymidine kinase gene (HSV-tk) delivery by retrovirus-producing cells and DNA/liposome complexes for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colorectal adenocarcinoma cells. After in vitro determination of the best transduction conditions, rats were treated with multiple intraperitoneal injections of plasmid DNA containing one or two copies of CMV-driven HSV-tk gene (pCMV-TK and p(CMV-TK)₂, respectively) associated with Lipofect-AMINE, each injection being followed by a Ganciclovir (GCV) course. Animals treated by DNA/liposome complexes and GCV or with retrovirus-producing cells and GCV snowed a similar increase of survival as compared to the control group. After DNA/liposome injections, expression of the tk transgene was detected in tumor nodes (epiploon) and also in liver, lung, spleen, bowels and brain. The expression was not homogeneous throughout the different organs and most likely reflected the transfection of only a limited number of cells.

Keywords

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