Cancer gene therapy by direct tumor injections of a nonviral T7 vector encoding a thymidine kinase gene

Human Gene Therapy
X ChenD Platika

Abstract

Previously, we described a nonviral cytoplasmic gene therapy vector system based on the T7 autogene concept. This system has been shown to achieve rapid and high levels of gene expression in a variety of animal cells and tissues. To test the utility of the system in vivo tumor ablation, a T7 cancer gene therapy plasmid vector, pT7T7/T7TK, was constructed. This nonviral vector contains a T7 autogene, T7T7, and a human herpes simplex virus thymidine kinase (HSV-TK) gene driven by a second T7 promoter (T7TK). When co-transfected with T7 RNA polymerase (T7 RNAP) into cultured human osteosarcoma 143B cells, abut 10-20% of the cells were found to express HSV-TK, and more than 90% of the cells were killed in the presence of 1 microM ganciclovir (GCV) within 4 days after DNA transfection. The increase in killing above the transfection frequency is due to a "bystander" effect among transfected and untransfected 143B cells. Direct injections of pT7T7/T7TK into 143B tumors grown in nude mice resulted in TK gene expression in tumor cells located near the injection sites as revealed by the immunohistochemical staining. Repeated tumor injections of the pT7T7/T7TK vector and intraperitoneal (i.p.) injections of GCV resulted in inhibition of t...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Nov 1, 1990·Nature·B MossT R Fuerst
Feb 21, 1990·Journal of the National Cancer Institute·F L Moolten, J M Wells
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·S H ChenS L Woo
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M CarusoD Klatzmann
Apr 1, 1993·Cancer·K Seiter, N Kemeny
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·B G FoxE Münck
Oct 20, 1996·Human Gene Therapy·T Marcel, J D Grausz

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Citations

Oct 13, 2006·Journal of Cancer Research and Clinical Oncology·Crispin R DassPeter F M Choong
Nov 24, 1999·Human Gene Therapy·M BrissonL Huang
Jan 25, 2002·Medicine·Danuta Balicki, Ernest Beutler
Dec 24, 2005·Expert Opinion on Drug Delivery·Alain Rolland
May 21, 1999·Drug Metabolism Reviews·D J WaxmanY Jounaidi
Apr 3, 2008·The Journal of Pharmacy and Pharmacology·Crispin R Dass, Peter F M Choong
Jul 14, 2006·Critical Reviews in Oncology/hematology·Eugene T H EkPeter F M Choong
Feb 19, 2003·Biochemical and Biophysical Research Communications·Risako NakanoTadanori Mayumi

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