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=== Gene electroporation === [[Image:Electrogenetransfer.JPG|thumb|500x500px]] Application of electric pulses of sufficient strength to the cell causes an increase in the trans-membrane potential difference, which provokes the membrane destabilization. Cell membrane permeability is increased, and otherwise non-permeant molecules enter the cell.<ref name="kotnik2000">{{cite journal | vauthors = Kotnik T, Miklavcic D | title = Analytical description of transmembrane voltage induced by electric fields on spheroidal cells | journal = Biophysical Journal | volume = 79 | issue = 2 | pages = 670β679 | date = August 2000 | pmid = 10920001 | pmc = 1300967 | doi = 10.1016/S0006-3495(00)76325-9 | bibcode = 2000BpJ....79..670K }}</ref><ref name="sweeney2018">{{cite journal | vauthors = Sweeney DC, Weaver JC, Davalos RV | title = Characterization of Cell Membrane Permeability In Vitro Part I: Transport Behavior Induced by Single-Pulse Electric Fields | journal = Technology in Cancer Research & Treatment | volume = 17 | pages = 1533033818792491 | date = January 2018 | pmid = 30236040 | pmc = 6154305 | doi = 10.1177/1533033818792491 }}</ref> Although the mechanisms of gene electrotransfer are not yet fully understood, it was shown that the introduction of DNA only occurs in the part of the membrane facing the cathode and that several steps are needed for successful transfection: electrophoretic migration of DNA towards the cell, DNA insertion into the membrane, translocation across the spoke membrane, migration of DNA towards the nucleus, transfer of DNA across the nuclear envelope and finally gene expression.<ref name="satkauskas2002">{{cite journal | vauthors = Satkauskas S, Bureau MF, Puc M, Mahfoudi A, Scherman D, Miklavcic D, Mir LM | title = Mechanisms of in vivo DNA electrotransfer: respective contributions of cell electropermeabilization and DNA electrophoresis | journal = Molecular Therapy | volume = 5 | issue = 2 | pages = 133β40 | date = February 2002 | pmid = 11829520 | doi = 10.1006/mthe.2002.0526 | doi-access = free }}</ref> There are a number of factors that can influence the efficiency of gene electrotransfer, such as: temperature, parameters of electric pulses, DNA concentration, electroporation buffer used, cell size and the ability of cells to express transfected genes.<ref name="gehl2003">{{cite journal | vauthors = Gehl J | s2cid = 16742681 | title = Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research | journal = Acta Physiologica Scandinavica | volume = 177 | issue = 4 | pages = 437β47 | date = April 2003 | pmid = 12648161 | doi = 10.1046/j.1365-201X.2003.01093.x }}</ref> In ''[[in vivo]]'' gene electrotransfer, DNA diffusion through extracellular matrix, properties of tissue, and overall tissue conductivity may be crucial.<ref name="miklavcic1998">{{cite journal | vauthors = Miklavcic D, Beravs K, Semrov D, Cemazar M, Demsar F, Sersa G | title = The importance of electric field distribution for effective in vivo electroporation of tissues | journal = Biophysical Journal | volume = 74 | issue = 5 | pages = 2152β8 | date = May 1998 | pmid = 9591642 | pmc = 1299558 | doi = 10.1016/S0006-3495(98)77924-X | bibcode = 1998BpJ....74.2152M }}</ref>
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