Gene therapy for oral cancer: efficient delivery of a 'suicide gene' to murine oral cancer cells in physiological milieu.
Gene therapy is a new therapeutic modality in which defective genes are replaced with functional ones, or genes are delivered that can specifically kill cancer cells. Efficient gene delivery is an important component of gene therapy approaches. Potential safety problems with viral vectors necessitate the development of efficient nonviral vectors. DNA complexes with synthetic cationic liposomes or polymers constitute a simple means of transferring DNA into target cells. Gene delivery mediated by many nonviral vectors, however, is inhibited by serum components, and this is expected to limit the efficiency of gene delivery in vivo. In this study, the authors examined two novel gene transfection reagents, Metafectene and GeneJammer, for their ability to deliver a reporter gene to SCCVII murine squamous cell carcinoma cells in the presence of high concentrations of mouse serum. After establishing conditions that achieved significant gene delivery, the authors introduced the Herpes Simplex Virus Thymidine kinase (HSV-tk) gene into the cells using the cationic liposome reagent, Metafectene, followed by the administration of ganciclovir. After seven days of incubation, 90 percent and 82 percent cytotoxicity was observed in 0 percent and 60 percent mouse serum, respectively. The authors' observations suggest that Metafectene may be useful for the gene therapy of oral squamous cell carcinoma in a murine model involving the induction of oral tumors by SCCVII cells.
Young
Mark
M
University of the Pacific Arthur A. Dugoni School of Dentistry, San Francisco, CA, 94115, USA.
Overlid
Nathan
N
Konopka
Krystyna
K
Düzgünes
Nejat
N
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001769:Blood; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy; D003587:Cytomegalovirus / Q000235:genetics; D004337:Drug Carriers; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D008055:Lipids; D008081:Liposomes; D051379:Mice; D009062:Mouth Neoplasms / Q000235:genetics / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection
D000998:Antiviral Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; C500466:metafectene; D013937:Thymidine Kinase; D015774:Ganciclovir