Inovio Scientific Publications
An extensive list of scientific papers documenting the utility of electroporation-based DNA delivery have been written by Inovio scientists or scientists associated with collaborating organizations and published in peer-reviewed journals:
Inovio Scientific Papers: DNA Delivery & Electroporation
Rice, J., Ottensmeier, C.H., Stevenson, F. DNA vaccines: precision tools for activating effective immunity against cancer. Nature Reviews Cancer, 108-120 Vol 8, Feb. 2008
"...for clinical trials of vaccines against cancer, initial enthusiasm turned to frustration with an apparent failure to translate promising vaccine designs from preclinical models into human subjects. The problem lay with delivery of DNA, and might now be solved by EP (electroporation), which is a known way of increasing transfection in vitro and is now successfully applied in vivo."
"EP (electroporation) appears to have surmounted the hurdle required to translate DNA vaccination into the clinic..."
Ahlen, G., Söderholm, J., Tjelle, T., Kjeken, R., Frelin, L., Höglund, U., Blomberg, P., Fons, M., Mathiesen, I., and Sällberg, M. In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells.1 The Journal of Immunology, 179:4741-4753, 2007.
"...in vivo (electroporation) greatly enhanced DNA uptake, protein expression levels...and the strength of the primed immune responses."
Luckay, A., Sidhu, M. K., Kjeken, R., Megati, S., Chong, S., Roopchand, V., Garcia-Hand, D., Abdullah, R., Braun, R., Montefiori, D. C., Rosati, M., Felber, B. K., Pavlakis, G. N., Mathiesen, I., Israel, Z. R., Eldridge, J. H., and Egan, M. A. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. Journal of Virology, Vol. 81, No. 10 P. 5257-5269, 2007.
"...important implications for the design and development of an efficacious therapeutic vaccine for the treatment of HIV-1 infection."
Capone, S., Zampaglione, I., Vitelli, A., Pezzanera, M., Kierstead, L., Burns, J., Ruggeri, L., Arcuri., Cappelletti, M., Meola, A., Ercole, B.B., Tafi, R., Santini, C., Luzzago, A., Fu, T., Colloca., Ciliberto, G., Cortese, R., Nicosia, A., Fattori, E., and Folgori, A. Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. The Journal of Immunology, 177: 7462-7471, 2006.
"...showed that gene electrotransfer (GET) of a novel candidate DNA vaccine ... induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques..."
Ulmer, J.B., Wahren, B., and Liu, M.A. Gene-based vaccines: recent technical and clinical advances. Trends in Molecular Medicine, Vol. 12 No. 5, May 2006.
"A particularly effective physical delivery technology uses electroporation (EP)... Owing to the physical nature of this delivery methodology, this approach should be effective for DNA delivery in large animals, including humans (issues of safety, tolerability and practicability aside)...EP markedly increases the extent of both antibody and T-cell responses in non-human primates, producing levels of antigen-specific CD8C T cells as high as 5% of total T cells [2]. This level of immunogenicity in primates is usually obtained only by using live viral vectors such as recombinant adenovirus."
Capone, S., Zampaglione, I., Vitelli, A., Pezzanera, M., Kierstead, L., Burns, J., Ruggeri, L., Arcuri, M., Cappelletti, M., Meola, A., Ercole, B. B., Tafi, R., Sanitini, C., Luzzago, A., Fu, T., Colloca, S., Ciliberto, G., Cortese, R., Nicosia, A., Fattori, E., and Folgori, A. Electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. The Journal of Immunology, 177:7462-7471, 2006.
L.Z., Zhang H., Fan X., Zhang Y., Huang J., Liu Q., Tjelle T.E., Mathiesen I., Kjeken R., Xiong S. DNA electroporation prime and protein boost strategy enhances humoral immunity of tuberculosis DNA vaccines in mice and non-human primates. Vaccine. 24(21):4565-8, May 22 2006.
Tjelle T.E., Salte R., Mathiesen I., Kjeken R. A novel electroporation device for gene delivery in large animals and humans. Vaccine 24(21):4667-70 May 22 2006.
Grønevik E., Mathiesen I., Lømo T. Early events of electroporation-mediated intramuscular DNA vaccination potentiate Th1-directed immune responses. J Gene Med.,7 (9):1246-54. Sep. 2005.
Pierog J., Gazdhar A., Stammberger U., Gugger M., Hyde S., Mathiesen I., Grodzki T., Schmid R.A. Synergistic effect of low dose cyclosporine A and human interleukin 10 over expression on acute rejection in rat lung allotransplantation. Eur J Cardiothorac Surg. 27(6):1030-5 Jun 2005.
Buchan S., Grønevik E., Mathiesen I., King C.A., Stevenson F.K., Rice J. Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen. Journal of Immunology. 174(10):6292-8; May 15 2005.
Grønevik E., Von Steyern F.V., Kalhovde J.M., Tjelle T.E., Mathiesen I. Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle. J Gene Med. 7(2):218-27. Oct 2004.
Scheerlinck J.P., Karlis J., Tjelle T.E., Presidente P.J., Mathiesen I., Newton S.E. In vivo electroporation improves immune responses to DNA vaccination in sheep. Vaccine. 22(13-14):1820-5. Apr 16 2004.
Tjelle T.E., Corthay A., Lunde E., Sandlie I., Michaelsen T.E., Mathiesen I., Bogen B. Monoclonal antibodies produced by muscle after plasmid injection and electroporation. Mol Ther. 9(3):328-36. Mar 2004.
Grønevik E., Tollefsen S., Sikkeland L.I., Haug T., Tjelle T.E., Mathiesen I. DNA transfection of mononuclear cells in muscle tissue. J Gene Med. 5(10):909-17. Oct 2003.
Heller, R. Delivery of plasmid DNA using in vivo electroporation. Preclinica, Vol. 1, No. 4, P. 198-208, September 2003.
Tollefsen S., Vordermeier M., Olsen I., Storset A.K., Reitan L.J., Clifford D., Lowrie D.B., Wiker H.G., Huygen K., Hewinson G., Mathiesen I., Tjelle T.E. DNA injection in combination with electroporation: a novel method for vaccination of farmed ruminants. Scand J Immunol. 7(3):229-38. Mar 5 2003.
Rabussay, R., Dev, N. B., Fewell, J., Smith, L.C., Widera, G., Zhang, L. Enhancement of therapeutic drug and DNA delivery into cells by electroporation. Journal of Physics D: Applied Physics 36(4):348-363, 2003.
Lucas, M. L., and Heller, R., IL-12 Gene therapy using an electrically mediated nonviral approach reduces metastatic growth of melanoma. DNA and Cell Biology Vol 22, Number 12, Pp. 755-763, 2003.
Tollefsen S., Tjelle T., Schneider J., Harboe M., Wiker H., Hewinson G., Huygen K., Mathiesen I. Improved cellular and humoral immune responses against mycobacterium tuberculosis antigens after intramuscular DNA immunization combined with muscle electroporation. Vaccine. 20(27-28):3370-8. Sep 10 2002.
Zhang, L., Nolan, E., Kreitschitz, S., and Rabussay, D. P. Enhanced delivery of naked DNA to the skin by non-invasive in vivo electroporation. Biochemical et Biophysical Acta 1572:1-9, 2002.
Lucas, M.L., Heller, L., Coppola, Domenico, C., Heller, R. IL-12 Plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Molecular Therapy, Vol. 5, No. 6 p. 668-675, June 2002.
Babiuk S., Baca-Estrada M. E., Foldvari, M., Storms, M., Rabussay, D., Widera, G., Babiuk, Lorne A. Electroporation improves the efficacy of DNA vaccines in large animals. Vaccine 20:3399-3408, 2002.
Rabussay, D. P., Widera, G. Electroporation mediated drug & DNA delivery in oncology and gene therapy. Drug Delivery Technology 2(3):34-40, 2002.
Moens, U., Mathiesen, I., Ghelue, M. V., Rekvig, O, P. Green fluorescent protein modified to bind DNA initiates production of anti-DNA antibodies when expressed in vivo. Mol Immunol 38(7):505-14, Jan 2002
Goto, T., Nishi, T., Tamura, T., Dev, S.B., Takeshima, H., Kochi, M., Yoshizato, K., Kuratsu, J-I., Sakata, T., Hofmann, G.A. and Ushio, Y. Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene. PNAS, 97(1):354-359, 2000.
Keating, A., Nolan, E., Filshie, R. and Dev. S.B. Ex vivo stromal cell electroporation of Factor IX cDNA for treatment of hemophilia B. In: Methods in Molecular Medicine Vol. 37, Ch 28, pp. 359-368, M.J. Jaroszeski, R. Heller, and R. Gilbert, eds., Humana Press, Inc., Totowa, NJ, 2000.
Widera, G., Austin, M., Rabussay, D., Goldbeck, C., Barnett, S.W., Chen, M., Leung, L., Otten, G.R., Thudium, K., Selby, M.J. and Ulmer, J.B. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. The Journal of Immunology, 164:4635-4640, 2000.
Yoshizato, K., Nishi, T., Goto, T., Dev, S.B., Takeshima, H., Kino, T., Tada, K., Kumura, T., Shiraishi, S., Kochi, M., Kuratsu, J-I., Hofmann, G.A. and Ushio, Y. Gene delivery with optimized electroporation parameters shows potential for treatment of gliomas. Intl. J. of Oncology, 16:899-905, 2000.
Zhang, L. In vivo skin-targeted gene delivery by pulsed electric field. In: Methods in Molecular Medicine Vol. 37, Ch. 35, pp. 473-488, M.J. Jaroszeski, R. Heller, and R. Gilbert, eds., Humana Press, Inc., Totowa, NJ, 2000.
Rizzuto G., Cappelletti M., Maione D., Savino R., Lazzaro D., Costa P., Mathiesen I., Cortese R., Ciliberto G., Laufer R., La Monica N., Fattori E. Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation. Proc Natl Acad Sci U S A; 96(11):6417-22. May 25 1999.
Mathiesen I. Electropermeabilization of skeletal muscle enhances gene transfer in vivo. Gene Therapy 6(4):508-14 Apr 1999.
Nishi, T., Dev, S.B., Yoshizato, K., Kuratsu, J-I., Ushio, Y. Treatment of cancer using pulsed electric field in combination with chemotherapeutic agents or genes. Human Cell 10(1):81-86, 1997.
Zhang, L., Li, L., Hofmann, G.A. and Hoffman. Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: An approach to gene therapy of skin aging and other diseases. Biochemical and Biophysical Research Communications, 220:633-636, 1996.
Matthews, K.E., Dev, S.B., Toneguzzo, F. and Keating, A. Electroporation for gene therapy. In: Methods in Molecular Biology, Vol 48, Ch. 22, pp. 273-280, J.A. Nickoloff, ed., Humana Press, Inc., Totowa, NJ, 1995.
Inovio Scientific Papers: General Electroporation Applications
Rabussay, D .P., Nanda, G.S., and Goldfarb, P. M., Enhancing the effectiveness of drug-based cancer therapy by electroporation (electropermeabilization) Technology in Cancer Research & Treatment Vol 1. Number 1, 2002.
Zhang, L., Rabussay, D. P. Clinical evaluation of safety and human tolerance of electrical sensation induced by electric fields with non-invasive electrodes. Bioelectrochemistry 56:233-236, 2002.
Dev, S.B., Rabussay, D.P., Widera, G. and Hofmann, G.A. Medical applications of electroporation. IEEE Transactions on Plasma Science, 28(1):206-223, 2000.
Hofmann, G.A. Instrumentation and electrodes for in vivo electroporation. Methods in Molecular Medicine Vol. 37, Ch. 2, pp. 37-61, M.J. Jaroszeski, R. Heller, and R. Gilbert, eds., Humana Press, Inc., Totowa, NJ, 2000.
Rabussay, D. and Kornhauser, S. Frequently asked questions about electroporation therapy. Medical Electronics, pp. 1-5, 1998.
Dev, S.B. and Rabussay, D.P. Electroporation therapy marches on. Cancer Watch, 7:123-124, 1998.
Dev, S.B. and Hofmann, G.A. Clinical applications of electroporation. Electrical manipulation of cells. pp. 185-199, P.T. Lynch, and M.R. Davey (eds.), Chapman & Hall, New York, 1996.
Hofmann, G.A. Instrumentation. Methods in Molecular Biology: Electroporation protocols for microorganisms. Vol. 47, pp. 27-45, J.A. Nickoloff, ed., Humana Press, Inc., Totowa, NJ, 1995.
Hofmann, G.A. Cells in electric fields. Physical and practical electronic aspects of electro cell fusion and electroporation. Electroporation and Electrofusion in Cell Biology, pp. 389-407, E. Neumann, A.E. Sowers and C.A. Jordan, eds., Plenum Press, NY, 1989.