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 mug/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. (C) 2001 Elsevier Science.