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- Title
Cationic lipid-based delivery system for systemic cancer gene therapy.
- Authors
Anwer, Khursheed; Meaney, Clare; Kao, Grace; Hussain, Nasir; Shelvin, Robert; Earls, Rosa M; Leonard, Pat; Quezada, Abraham; Rolland, Alain P; Sullivan, Sean M
- Abstract
A cationic lipid-based gene delivery system composed of N-[(1-(2,3-dioleyloxy)propyl)]-N-N-N-trimethylammonium chloride and cholesterol, at a 4:1 molar ratio, was developed for systemic administration. Plasmid biodistribution and expression were characterized in syngeneic mouse tumor model squamous cell carcinoma VII cells. A reporter gene expression plasmid was used for biodistribution of plasmid and expression. The results showed that lungs and primary tumors were transfected. Fluorescence microscopy showed that fluorescent-labeled transfection complexes were passively targeted to the tumor vasculature and that the endothelial cells internalized the plasmid. Transgene expression was characterized based on duration of expression and dosing schedule. In viva gene transfer with an interleukin-12 expression plasmid yielded protein levels in blood, lungs, and primary tumor after intravenous administration. Efficacy studies showed that 15 µg of interleukin-12 plasmid was sufficient to produce a gene-specific inhibition of primary tumor growth. These results characterize the vascularity of the tumor model, characterize the in viva gene transfer properties of the plasmid-based gene delivery system, and show that the transgene expression level was sufficient to elicit a biological response by inhibiting tumor growth.
- Subjects
LIPIDS; CANCER treatment; GENE therapy; SQUAMOUS cell carcinoma
- Publication
Cancer Gene Therapy, 2000, Vol 7, Issue 8, p1156
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700218