Intravenous delivery of naked plasmid DNA for in vivo cytokine expression.
We previously demonstrated that electroporation-mediated cytokine gene delivery into muscle is an effective approach for long-term systemic delivery of cytokines. Here we show that hydrodynamics-based gene delivery into mice by intravenous administration of naked plasmid DNA is a more efficient procedure for expressing cytokines in vivo. A large volume of Ringer's solution containing an interleukin-10 (IL-10) expression plasmid pCAGGS-IL10 was rapidly injected into the tail vein of mice. Serum IL-10 levels increased in a dose-dependent manner with a saturation level (50.8 +/- 12.1 microg/ml) 10,000-fold higher than we obtained by the electroporation-mediated method. High levels of serum IL-10 were sustained for at least 2 weeks following a single injection. These results demonstrate that hydrodynamics-based gene delivery could induce sustained high-level expression of cytokines, which would be useful for further studies of cytokine function in vivo and the development of novel immunotherapeutic strategies for systemic cytokine gene therapy.
Jiang
J
J
Division of Stem Cell Regulation Research (G6), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yamato
E
E
Miyazaki
J
J
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D014162:Transfection
D016207:Cytokines; D016753:Interleukin-10