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.

[1]  B. Carter,et al.  Adeno-associated virus vectors , 1992, Current Biology.

[2]  J. Wolff,et al.  Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor‐mediated process , 2000, The journal of gene medicine.

[3]  J. Northrop,et al.  Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. Kishimoto,et al.  Anticytokine therapy in autoimmune diseases. , 1999, Internal medicine.

[5]  J. Miyazaki,et al.  Systemic delivery of interleukin 10 by intramuscular injection of expression plasmid DNA prevents autoimmune diabetes in nonobese diabetic mice. , 1998, Human gene therapy.

[6]  J. Wang,et al.  Consideration of cytokines as therapeutics agents or targets. , 2000, Current pharmaceutical design.

[7]  H. Okamura,et al.  Interleukin-18 regulates both Th1 and Th2 responses. , 2001, Annual review of immunology.

[8]  Dexi Liu,et al.  Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA , 1999, Gene Therapy.

[9]  Daniel G. Miller,et al.  Use of retroviral vectors for gene transfer and expression. , 1993, Methods in enzymology.

[10]  W. Arend.  Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist. , 2001, Seminars in arthritis and rheumatism.

[11]  N. Yang,et al.  In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Qiao,et al.  Direct gene transfer into donor hearts at the time of harvest. , 1995, The Journal of thoracic and cardiovascular surgery.

[13]  Yamamura Ken-ichi,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector , 1991 .

[14]  K. Berkner.  Expression of heterologous sequences in adenoviral vectors. , 1992, Current topics in microbiology and immunology.

[15]  P. Alstergren.  Cytokines in temporomandibular joint arthritis. , 2008, Oral diseases.

[16]  L. Shapiro,et al.  A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. , 1995, Journal of immunology.

[17]  J. Wolff,et al.  High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. , 1999, Human gene therapy.

[18]  H. Niwa,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector. , 1991, Gene.

[19]  J. Wilson,et al.  Gene therapy: adenovirus vectors. , 1993, Current opinion in genetics & development.

[20]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Soria,et al.  IL‐12 indirectly enhances proliferation of 5‐FU‐treated human hematopoietic peripheral blood CD34+ cells , 1998, American journal of hematology.

[22]  G. Acsadi,et al.  Direct gene transfer into mouse muscle in vivo. , 1990, Science.

[23]  H. Aihara,et al.  Gene transfer into muscle by electroporation in vivo , 1998, Nature Biotechnology.

[24]  Jaroszeski,et al.  In vivo gene delivery by electroporation. , 1999, Advanced drug delivery reviews.