Electroporative Gene Transfer

  • Marco SchmeerEmail author
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)


Membrane electroporation (MEP) uses short high-voltage pulses to render cell membranes transiently porous and therewith permeable to otherwise impermeable substances. This technique was first described, in vitro, by Neumann in 1982 ( 1 ). In vivo, this method is restricted to solid tissues accessible to the electrodes used to apply the electric field pulses. Electroporation of cell tissue gains increasing importance especially in clinical applications such as electrochemotherapy (ECT) of, e.g., skin tumors, and for gene therapy ( 2, 3, 4 ). The various applications of MEP include, in addition to the direct functional transfer of genes (electrotransfection, electrogenetransfer) and drugs, the release of proteins, and the electrotransfer of ionic dyes into cells (5). But, nevertheless, the mechanism of pore opening and resealing as well as the transfer, especially of DNA, is not yet completely understood.


Electrogenetransfer electrotransfection membrane electroporation membrane pores 


  1. 1.
    Neumann, E., Schaefer-Ridder, M., Wang, Y., Hofschneider, P.H. (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1, 1982, 841–845.PubMedGoogle Scholar
  2. 2.
    Mir, L.M., Tounekti, O., Orlowski, S. (1996) Bleomycin: revival of an old drug. Gen. Pharmacol. 27, 745–748.PubMedCrossRefGoogle Scholar
  3. 3.
    Heller, R., Jaroszeski, M.L., Glass, L.E., Messina, J.L., Rapaport, D.P., De Conti, R.C., Frenske, N.A., Gilbert, R.A., Mir, L.M., Reintgen, D.S. (1996) Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using chemoelectrotherapy. Cancer, 77, 964–971.PubMedCrossRefGoogle Scholar
  4. 4.
    Heller, R., Jaroszeski, M.L., Glass, L.E., Messina, J.L., Rapaport, D.P., De Conti, R.C., Frenske, N.A., Gilbert, R.A., Mir, L.M., Reintgen, D.S. (1996) Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using chemoelectrotherapy. Cancer, 77, 964–971.PubMedCrossRefGoogle Scholar
  5. 5.
    Neumann, E., Tönsing, K., Kakorin, S., Budde, P., Frey, J. (1998) Mechanism of electroporative dye uptake by mouse B cells. Biophys. J. 74, 1998, 98–108.PubMedCrossRefGoogle Scholar
  6. 6.
    Neumann, E. (1991) Membrane electroporation and direct gene transfer. Bioelectrochem. Bioenerg. 28, 247–267.CrossRefGoogle Scholar
  7. 7.
    Schmeer, M., Seipp, T., Pliquett, U., Kakorin, S., Neumann, E. (2004) Mechanism for the conductivity changes caused by membrane electroporation of CHO cell – pellets. Phys. Chem. Chem. Phys. 6, 5564–5574.CrossRefGoogle Scholar
  8. 8.
    Pliquett, U., Elez, R., Piiper, A., Neumann, E. (2004) Electroporation of subcutaneous mouse tumor by rectangular and trapezium high voltage pulses. Bioelectrochemistry 62, 83–93.PubMedCrossRefGoogle Scholar
  9. 9.
    Neumann, E., Boldt, E. (1990) Membrane electroporation: the dye method to determine the cell membrane conductivity. In Nicolau, C., Chapman, D. (eds.) Horizons in Membrane Technology, Progress in Clinical and Biological Research. Wiley-Liss, New York, pp. 69–83.Google Scholar
  10. 10.
    Miklavcic, D.,Semrov, D., Mekid, H., Mir, L.M. (2000) A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim. Biophys. Acta 1523, 73–83.PubMedCrossRefGoogle Scholar
  11. 11.
    Nishi, T., Kimio, Y., Yanashiro, S., Takeshima, H. Sato, K., Hamada, K., Kitamura, I., Yoshikura, T., Saya, H., Kuratsu, J., Ushio, Y. (1996) High-efficiency in vivo gene transfer using intaarterial plasmid DNA injection following in vivo electroporation. Cancer Res. 56, 1050–1055.PubMedGoogle Scholar
  12. 12.
    Rols, M.P., Delteil, C., Golzio, M., Dumond, P., Cros, S., Teissie, J. (1998) In vivo electrically mediated protein end gene transfer in murine and gene transfer in murine melanoma. Nat. Biotechnol. 16(2), 168–171.PubMedCrossRefGoogle Scholar
  13. 13.
    Goto, T., Nishi, T., Tamura, T., Dev, S.B., Takeshima, H., Kochi, M., Yoshizato, K., Kuratsu, J.-I., Sakata, T., Hofmann, G.A., Ushio, Y. (2000) Highly effective electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene. PNAS 97(1), 354–359.PubMedCrossRefGoogle Scholar
  14. 14.
    Lohr, F., Lo, D.Y., Zaharoff, D.A., Hu, K., Zhang, X., Li, Y., Zhao, Y., Dewhirst, M.W., Yuan, F., Li, C.-Y. (2001) Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation. Cancer Res. 61, 3281–3284.PubMedGoogle Scholar
  15. 15.
    Zhang, G.-H., Tan, X.-F., Shen, D., Zhao, S.-Y., Shi, Y.-Y., Jin, C.-K., Guo, Y.-H., Chen, K.-H., Tang, J. (2003) Gene expression and antitumor effect following im electroporation delivery of human interferon α2 gene. Acta Pharmacol. Sin. 24(9), 891–896.PubMedGoogle Scholar
  16. 16.
    Elez, R., Piiper, A., Kronenberger, B., Kock, M., Brendel, M., Hermann, E., Pliquett, U., Neumann, E., Zeuzem, S. (2003) Tumor regression by combination antisense therapy against Plk1 and Bcl-2. Oncogene 22, 69–80.PubMedCrossRefGoogle Scholar
  17. 17.
    Cemazar, M., Wilson, I., Dachs, G.U., Tozer, G.M., Sersa, G. (2004) Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution. BMC Cancer 4:81,
  18. 18.
    Buchan, S., Gronevik, E., Mathiesen, I., King, C.A., Stevenson, F.K., Rice, J. (2005) Electroporation as a “Prime/Boost” Strategy for Naked DNA Vaccination against Tumor Antigen1. J. Immunol. 174, 6292–6298.PubMedGoogle Scholar
  19. 19.
    Maucksch, C., Hoffmann, F., Schleef, M., Aneja, M.K., Rosenecker, J., Rudolph, C. (2005) In vitro transfection efficiency of concatameric plasmid DNA using nonviral transfection methods. Abstract book of the 13th Annual Congress of the European Society of Gene Therapy, p. 80.Google Scholar
  20. 20.
    Tjelle, T.E., Salte, R., Mathiesen, I., Kjeken, R. (2006) A novel electroporation device for gene delivery in large animals and humans. Vaccine 24, 4667–4670.PubMedCrossRefGoogle Scholar
  21. 21.
    Pliquett, U., Gift, E.A., Weaver, J.C. (1996) Determination of the electric field and anomalous heating caused by exponential pulses with aluminum electrodes in electroporation experiments. Bioelectrochem. Bioenerg. 39, 39–53.CrossRefGoogle Scholar
  22. 22.
    Gehl, J., Sorensen, T.H., Nielsen, K., Raskmark, P., Nielsen, S.L., Skovsgaard, T., Mir, L.M. (1999) In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys. Acta 1428, 233–240.PubMedCrossRefGoogle Scholar
  23. 23.
    Neumann, E., Pliquett, U., Seipp, T., Schmeer, M. (2003) Biokompatible elektroden für in vivo elektroporation zur wirkstoffzufuhr, Utility model, No. 203 02 861.9.Google Scholar
  24. 24.
    Pliquett, U., Schmeer, M., Seipp, T., Neumann, E. (2002) Fast recovery process after electroporation. IFMBE Proc. 3(1), 98–99.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.PlasmidFactory GmbH & Co.Bielefeld

Personalised recommendations