Editing Electroporation (section)

==Medical applications==
{{Main|Irreversible electroporation}}

The first medical application of electroporation was used for introducing poorly permeant anti-cancer drugs into tumor nodules.<ref name="pmid1723647">{{cite journal | vauthors = Mir LM, Belehradek M, Domenge C, Orlowski S, Poddevin B, Belehradek J, Schwaab G, Luboinski B, Paoletti C | title = [Electrochemotherapy, a new antitumor treatment: first clinical trial] | language = fr | journal = Comptes Rendus de l'Académie des Sciences, Série III  | volume = 313 | issue = 13 | pages = 613–8 | date = 1991 | pmid = 1723647 }}</ref> Gene electro-transfer soon became of interest because of its low cost, ease of implementation, and alleged safety. Viral vectors have since been found to have limitations in terms of immunogenicity and pathogenicity when used for DNA transfer.<ref name="pmid10636774">{{cite journal | vauthors = Marshall E | s2cid = 46362535 | title = Gene therapy death prompts review of adenovirus vector | journal = Science | volume = 286 | issue = 5448 | pages = 2244–5 | date = December 1999 | pmid = 10636774 | doi = 10.1126/science.286.5448.2244}}</ref>

[[Irreversible electroporation]] is being used and evaluated as [[Catheter ablation|cardiac ablation therapy]] to kill specific areas of heart muscle. This is done to treat [[Cardiac arrhythmia|irregularities of heart rhythm]]. A [[Cardiac catheterization|cardiac catheter]] delivers trains of high-voltage, ultra-rapid electrical pulses that form irreversible pores in cell membranes, resulting in cell death.<ref name="Tabaja_2023">{{cite journal |vauthors=Tabaja C, Younis A, Hussein AA, Taigen TL, Nakagawa H, Saliba WI, Sroubek J, Santangeli P, Wazni OM |date=September 2023 |title=Catheter-Based Electroporation: A Novel Technique for Catheter Ablation of Cardiac Arrhythmias |journal=JACC. Clinical Electrophysiology |volume=9 |issue=9 |pages=2008–2023 |doi=10.1016/j.jacep.2023.03.014 |pmid=37354168}}</ref>

===N-TIRE===
Non-thermal irreversible electroporation (N-TIRE) is a technique that treats many different types of tumors and other unwanted tissue. This procedure is done using small electrodes (about 1mm in diameter), placed either inside or surrounding the target tissue to apply short, repetitive bursts of electricity at a predetermined voltage and frequency. These bursts of electricity increase the resting transmembrane potential (TMP) so that nanopores form in the plasma membrane. When the electricity applied to the tissue is above the electric field threshold of the target tissue, the cells become permanently permeable from the formation of nanopores. As a result, the cells are unable to repair the damage and die due to a loss of homeostasis.<ref>{{cite book | vauthors = Garcia PA, Rossmeisl JH, Davalos RV | title = 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society | chapter = Electrical conductivity changes during irreversible electroporation treatment of brain cancer | s2cid = 4953213 | volume = 2011 | pages = 739–42 | year = 2011 | pmid = 22254416 | doi = 10.1109/IEMBS.2011.6090168 | isbn = 978-1-4577-1589-1 }}</ref> N-TIRE is unique to other tumor ablation techniques in that it does not create thermal damage to the tissue around it.

===Reversible electroporation===
In contrast, reversible electroporation occurs when the electricity applied with the [[Electrode|electrodes]] is below the target tissue's electric field threshold. Because the electricity applied is below the cells' threshold, it allows the cells to repair their [[phospholipid bilayer]] and continue with their normal cell functions. Reversible electroporation is typically done with treatments that involve inserting a drug or gene (or other molecule that is not normally permeable to the cell membrane) into the cell. Not all tissues have the same electric field threshold; therefore, to improve safety and efficacy, careful calculations need to be made prior to a treatment.<ref>{{cite book | vauthors = Garcia PA, Neal RE, Rossmeisl JH, Davalos RV | title = 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology | chapter = Non-thermal irreversible electroporation for deep intracranial disorders | s2cid = 9589956 | volume = 2010 | pages = 2743–6 | year = 2010 | pmid = 21095962 | doi = 10.1109/IEMBS.2010.5626371 | isbn = 978-1-4244-4123-5 }}</ref>

N-TIRE, when done correctly, only affects the target tissue. Proteins, the extracellular matrix, and critical structures such as blood vessels and nerves are all unaffected and left healthy by this treatment. This facilitates a more rapid replacement of dead tumor cells and a faster recovery.<ref>{{cite journal | vauthors = Garcia PA, Rossmeisl JH, Neal RE, Ellis TL, Olson JD, Henao-Guerrero N, Robertson J, Davalos RV | s2cid = 10958480 | title = Intracranial nonthermal irreversible electroporation: in vivo analysis | journal = The Journal of Membrane Biology | volume = 236 | issue = 1 | pages = 127–36 | date = July 2010 | pmid = 20668843 | doi = 10.1007/s00232-010-9284-z | citeseerx = 10.1.1.679.527 }}</ref>

Imaging technology such as [[CT scan|CT scans]] and [[Magnetic resonance imaging|MRIs]] are commonly used to create a 3D image of the tumor. Computed tomography is used to help with the placement of electrodes during the procedure, particularly when the electrodes are being used to treat tumors in the brain.<ref>{{cite book | vauthors = Neal RE, Garcia PA, Rossmeisl JH, Davalos RV | title = 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology | chapter = A study using irreversible electroporation to treat large, irregular tumors in a canine patient | s2cid = 24348785 | volume = 2010 | pages = 2747–50 | year = 2010 | pmid = 21095963 | doi = 10.1109/IEMBS.2010.5626372 | isbn = 978-1-4244-4123-5 }}</ref>

The procedure takes five minutes with a high success rate.<ref name = "Potter_2003" /> It may be used for future treatment in humans. One disadvantage of using N-TIRE is that the electricity delivered from the electrodes can stimulate muscle cells to contract, which could have lethal consequences, depending on the situation. Therefore, a paralytic agent must be used when performing the procedure. The paralytic agents that have been used in such research have risks<ref>{{Cite journal |last1=Deipolyi |first1=Amy R |last2=Golberg |first2=Alexander |last3=Yarmush |first3=Martin L |author-link3=Martin Yarmush |last4=Arellano |first4=Ronald S |last5=Oklu |first5=Rahmi |date=October 1, 2014 |title=Irreversible electroporation: evolution of a laboratory technique in interventional oncology |journal=Diagnostic and Interventional Radiology |volume=20 |issue=2 |pages=147–154 |doi=10.5152/dir.2013.13304 |pmc=4463294 |pmid=24412820 |doi-access=free}}</ref> when using anesthetics.

===H-FIRE===
High-frequency irreversible electroporation (H-FIRE) uses electrodes to apply bipolar bursts of electricity at a high frequency, as opposed to unipolar bursts of electricity at a low frequency. This type of procedure has the same tumor ablation success as N-TIRE. However, it has one distinct advantage: H-FIRE does not cause muscle contraction in the patient, and therefore, there is no need for a paralytic agent.<ref>{{cite journal | vauthors = Arena CB, Sano MB, Rossmeisl JH, Caldwell JL, Garcia PA, Rylander MN, Davalos RV | title = High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction | journal = BioMedical Engineering OnLine | volume = 10 | pages = 102 | date = November 2011 | pmid = 22104372 | pmc = 3258292 | doi = 10.1186/1475-925X-10-102 | doi-access = free }}</ref> Furthermore, H-FIRE has been demonstrated to produce more predictable ablations due to the lesser difference in the electrical properties of tissues at higher frequencies.<ref>{{cite journal | vauthors = Bhonsle SP, Arena CB, Sweeney DC, Davalos RV | title = Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses | journal = BioMedical Engineering OnLine | volume = 13 | pages = S3 | date = 27 August 2015 | issue = Suppl 3 | pmid = 26355870 | pmc =4565149 | doi = 10.1186/1475-925X-14-S3-S3 | doi-access = free }}</ref>

=== Drug and gene delivery ===
{{Further|Electrochemotherapy|gene electrotransfer}}
Electroporation can also be used to help deliver drugs or genes into the cell by applying short and intense electric pulses that transiently permeabilize cell membrane, thus allowing the transport of molecules otherwise not transported through a cellular membrane. This procedure is referred to as [[electrochemotherapy]] when the molecules to be transported are chemotherapeutic agents or [[gene electrotransfer]] when the molecule to be transported is DNA. Scientists from [[Karolinska Institute]] and the [[University of Oxford]] use electroporation of [[Exosome complex|exosomes]] to deliver [[SiRNA|siRNAs]], antisense oligonucleotides, chemotherapeutic agents, and proteins specifically to neurons after injecting them systemically (in blood). Because these exosomes can cross the [[blood brain barrier|blood-brain barrier]], this protocol could solve the problem of poor delivery of medications to the central nervous system and may potentially treat [[Alzheimer's disease]], [[Parkinson's disease]], and [[brain cancer]], among other conditions.<ref name="five2">{{cite journal | vauthors = El-Andaloussi S, Lee Y, Lakhal-Littleton S, Li J, Seow Y, Gardiner C, Alvarez-Erviti L, Sargent IL, Wood MJ | s2cid = 34413410 | title = Exosome-mediated delivery of siRNA in vitro and in vivo | journal = Nature Protocols | volume = 7 | issue = 12 | pages = 2112–26 | date = December 2012 | pmid = 23154783 | doi = 10.1038/nprot.2012.131 }}</ref>

Research has shown that shock waves could be used for pre-treating the cell membrane prior to electroporation.<ref>{{Cite journal| vauthors = Hu Q, Hossain S, Joshi RP |date=2018-06-25|title=Analysis of a dual shock-wave and ultrashort electric pulsing strategy for electro-manipulation of membrane nanopores|url=https://iopscience.iop.org/article/10.1088/1361-6463/aaca7a|journal=Journal of Physics D: Applied Physics|volume=51|issue=28|pages=285403|doi=10.1088/1361-6463/aaca7a|bibcode=2018JPhD...51B5403H|s2cid=125134522|issn=0022-3727}}</ref><ref>{{cite journal | vauthors = Hossain S, Abdelgawad A | title = Analysis of membrane permeability due to synergistic effect of controlled shock wave and electric field application | journal = Electromagnetic Biology and Medicine | volume = 39 | issue = 1 | pages = 20–29 | date = 2020-01-02 | pmid = 31868023 | doi = 10.1080/15368378.2019.1706553 | s2cid = 209446699 }}</ref> This synergistic strategy has shown to reduce external voltage requirement and create larger pores. Also, application of shock waves allow scope to target desired membrane site. This procedure allows to control the size of the pore.