Abstract
The development of new drugs depends greatly on their successful, efficient, low cost, and safe delivery into target cells or tissues. In the case of highly charged macromolecules such as nucleic acids, the therapeutic effectiveness is mainly limited by their bio-distribution within the tissue and the poor permeability of the plasma membrane of cells. For this purpose, electroporation appears as a promising method for nucleic acid delivery. Electroporation is a physical method of vectorization that consists of application of electric pulses on cells or tissues. Optimization of the pulses’ parameters leads to the transient permeabilization of the plasma membrane for molecules which otherwise cannot enter the cell. Therefore, the understanding of different principles of drug and gene delivery is necessary and needs to be taken into account according to the specificity of their delivery to tumors and/or normal tissues. This approach has been routinely used in cell biology for more than 30 years for cell transfection and in medicine in a number of clinics and hospitals through Europe to treat cutaneous cancers by increasing the toxicity of anticancer drugs (electrochemotherapy); it is also now under clinical trials for nucleic acid delivery (electrogenotherapy, electro-vaccination). The present chapter focuses on electrotransfer of nucleic acids, the nature of nucleic acids (plasmid DNA, mRNA, siRNA, LNA, etc.) which can be electrotransferred, and the mechanism of their electrotransfer.
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References
Aagaard L, Rossi JJ (2007) RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev 59:75–86
Aigner A (2007) Nonviral in vivo delivery of therapeutic small interfering RNAs. Curr Opin Mol Ther 9:345–352
Antov Y et al (2005) Electroendocytosis: exposure of cells to pulsed low electric fields enhances adsorption and uptake of macromolecules. Biophys J 88:2206–2223
Beebe SJ et al (2003) Diverse effects of nanosecond pulsed electric fields on cells and tissues. DNA Cell Biol 22:785–796
Bellard E et al (2012) Intravital microscopy at the single vessel level brings new insights of vascular modification mechanisms induced by electropermeabilization. J Control Release 163:396–403
Bodles-Brakhop AM et al (2009) Electroporation for the delivery of DNA-based vaccines and immunotherapeutics: current clinical developments. Mol Ther 17:585–592
Bumcrot D et al (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2:711–719
Chabot S et al (2012) LNA-based oligonucleotide electrotransfer for miRNA inhibition. Mol Ther 20:1590–1598
Chabot S et al (2015) Targeted electro-delivery of oligonucleotides for RNA interference: siRNA and antimiR. Adv Drug Deliv Rev 81:161–168
Corey DR (2007) Chemical modification: the key to clinical application of RNA interference? J Clin Invest 117:3615–3622
Daud AI et al (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903
Escoffre JM et al (2011) Electromediated formation of DNA complexes with cell membranes and its consequences for gene delivery. Biochim Biophys Acta 1808:1538–1543
Golzio M et al (2002) Direct visualization at the single-cell level of electrically mediated gene delivery. Proc Natl Acad Sci U S A 99:1292–1297
Golzio M et al (2010) Observations of the mechanisms of electromediated DNA uptake – from vesicles to tissues. Curr Gene Ther 10:256–266
Hibino M et al (1991) Membrane conductance of an electroporated cell analyzed by submicrosecond imaging of transmembrane potential. Biophys J 59:209–220
Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62
Jarm T et al (2010) Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert Rev Anticancer Ther 10:729–746
Mir LM et al (1998) Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer 77:2336–2342
Neumann E et al (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1:841–845
Paganin-Gioanni A et al (2011) Direct visualization at the single-cell level of siRNA electrotransfer into cancer cells. Proc Natl Acad Sci U S A 108:10443–10447
Portet T et al (2011) Insights into the mechanisms of electromediated gene delivery and application to the loading of giant vesicles with negatively charged macromolecules. Soft Matter 7:3872–3881
Rols MP (2010) Gene transfer by electrical fields. Curr Gene Ther 10:255
Rols MP, Teissie J (1990) Electropermeabilization of mammalian cells. Quantitative analysis of the phenomenon. Biophys J 58:1089–1098
Rosazza C et al (2011) The actin cytoskeleton has an active role in the electrotransfer of plasmid DNA in mammalian cells. Mol Ther 19:913–921
Sersa G et al (2008) Electrochemotherapy in treatment of tumours. Eur J Surg Oncol 34:232–240
Vaughan EE et al (2006) Intracellular trafficking of plasmids for gene therapy: mechanisms of cytoplasmic movement and nuclear import. Curr Gene Ther 6:671–681
Zuhorn IS et al (2007) Gene delivery by cationic lipid vectors: overcoming cellular barriers. Eur Biophys J 36:349–362
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Golzio, M., Rols, MP. (2017). Nucleic Acid Electrotransfer in Mammalian Cells: Mechanistic Description. In: Miklavčič, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-32886-7_21
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DOI: https://doi.org/10.1007/978-3-319-32886-7_21
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