The
jet-injection technology has developed as an applicable alternative to viral or liposomal gene delivery systems. In this study a novel, low-volume, 'high-speed jet injector' hand-held system was used for the direct gene transfer of naked
DNA into
tumors.
Lewis-lung carcinoma bearing mice were jet-injected with the
beta-galactosidase (LacZ), the green fluorescence (GFP) or the human
tumor necrosis factor alpha (
TNF-alpha) gene carrying vector plasmids. The animals received five
jet injections into the
tumor at a pressure of 3.0 bar, delivering 3--5 microl plasmid
DNA (1 microg
DNA/microl in water) per single
jet injection. The
jet injection of
DNA leads to a widespread expression pattern within
tumor tissues with penetration depths of 5--10 mm. Analysis of
tumor cryosections revealed moderate LacZ or GFP expression at 48 h and strong reporter gene expression 72 h and 96 h after
jet injection. The simultaneous
jet injection of the
TNF-alpha and LacZ carrying vectors demonstrated efficient expression and secretion of both the
cytokine, as well as LacZ expression within the
tumor 24 h, 48 h, 72 h, 96 h and 120 h after
jet injection. These studies demonstrate the applicability of
jet injection for the efficient in vivo gene transfer into
tumors for nonviral gene therapy of
cancer using minimal amounts of naked
DNA.