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Electroporation-Based Gene Therapy: Recent Evolution in the Mechanism Description and Technology Developments

  • Lluis M. Mir
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1121)

Abstract

Thirty years after the publication of the first report on gene electrotransfer in cultured cells by the delivery of delivering electric pulses, this technology is starting to be applied to humans. In 2008, at the time of the publication of the first edition of this book, reversible cell electroporation for gene transfer and gene therapy (nucleic acids electrotransfer) was at a cross roads in its development. In 5 years, basic and applied developments have brought gene electrotransfer into a new status. Present knowledge on the effects of cell exposure to appropriate electric field pulses, particularly at the level of the cell membrane, is reported here, as an introduction to the large range of applications described in this book. The importance of the models of electric field distribution in tissues and of the correct choice of electrodes and applied voltages is highlighted, as well as the large range of new specialized electrodes, developed also in the frame of the other electroporation-based treatments (electrochemotherapy). Indeed, electric pulses are now routinely applied for localized drug delivery in the treatment of solid tumors by electrochemotherapy. The mechanisms involved in DNA electrotransfer, which include cell electropermeabilization and DNA electrophoresis, are also surveyed: noticeably, the first molecular description of the crossing of a lipid membrane by a nucleic acid was reported in 2012. The progress in the understanding of cell electroporation as well as developments of technological aspects, in silico, in vitro and in vivo, have contributed to bring gene electrotransfer development to the clinical stage. However, spreading of the technology will require not only more clinical trials but also further homogenization of the protocols and the preparation and validation of Standard Operating Procedures.

Key words

Electropermeabilization Electroporation DNA electrotransfer Theory Electric pulses Gene transfer Nonviral gene therapy 

Notes

Acknowledgements

L.M. Mir acknowledges all his colleagues for stimulating discussions. The work of his team is conducted in the scope of the LEA EBAM (European Associated Laboratory on the Applications of the Electric pulses in Biology And Medicine). Activities are presently supported through grants of the ANR (IPSIOAT, INTCELL, MEMOVE) and of the ANSES (MARFEM).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lluis M. Mir
    • 1
    • 2
    • 3
  1. 1.Laboratoire de Vectorologie et Therapeutiques Anticancereuses, UMR, Univ Paris-SudVillejuifFrance
  2. 2.Laboratoire de Vectorologie et Therapeutiques Anticancereuses, CNRS, UMRVillejuifFrance
  3. 3.Laboratoire de Vectorologie et Therapeutiques Anticancereuses, Gustave Roussy, UMRVillejuifFrance

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