Electroporation therapeutic applications

It is noteworthy that some therapeutic applications, such as transcutaneous electrical neural stimulation, involve application to the skin of electric pulses of up to hundreds of volts [5], However, a safety limitation is the major concern associated with the use of electroporation, even though several reports indicated that the damage to the skin was mild and reversible [16,23]. The only skin alteration seen with electroporation was slight erythema that decreased within a few hours [34]. Patients submitted to electrochemotherapy seemed to tolerate well the application of 10,000 V/cm for 100 p,s square-wave pulses [35]. However, to avoid pain during electroporation, milder conditions such as lower voltage, shorter pulses, or improved electrode design could be used [36]. 

Expression of the therapeutic protein is enhanced by electroporation - the application of a small amount of electricity at the site of injection for a few milliseconds. This high-intensity electric field induces temporary and reversible breakdown of the plasma membrane allowing plasmids and other molecules to gain intracellular access [110]. This plasmid-based PA-inducible transgene regulating... 

The simplest nonviral gene transfer system in use for gene therapy is the injection of naked plasmid DNA (pDNA) into local tissues or the systemic circulation (88, 100). Naked DNA systems are composed of a bacterial plasmid that contains the cDNA of a reporter or therapeutic gene under the transcriptional control of various regulatory elements (101, 102). In recent years, work in several laboratories has shown that naked plasmid DNA (pDNA) can be delivered efficiently to cells in vivo either via electroporation, or by intravascular delivery, and has great prospects for basic research and gene therapy (101). Efficient transfection levels have also been obtained on direct application of naked DNA to the liver (103, 104), solid tumours (105), the epidermis (106), and hair follicles (106). 

It is already 40 years since the first, theoretical papers have been published on the possibility of high-frequency EMF to initiate reversible pores in plasma membranes. The recent advances in theoretical and experimental work, as well as application with therapeutic purposes, were summarized by Pakhomov et al. [16]. This method allows transport through the membrane of small ions and large molecules, which is otherwise impossible. The electric field required to achieve electroporation depends on duration of the pulse and the amplitude of the applied electric field. 

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