Impedance Changes as an Indicator of Successful Skin Electroporative DNA delivery

描述（由申请人提供）：在过去的15年里，电穿孔已经发展成为一种可行的体内DNA传递方法/技术。它已被研究作为DNA疫苗、癌症治疗和代谢性疾病管理的递送方法，在临床前研究中取得了很大成功。这些应用已经转化为临床试验；其中大部分仍在进行中。这种方法的主要复杂性是控制直流脉冲的应用，以便在目标组织中达到最大或期望的表达水平。并发症源于组织间的差异和其他因素，这些因素可能导致电脉冲治疗不足或过度治疗。目前，还没有办法控制脉冲的应用。本研究旨在探讨利用电阻抗作为控制电脉冲应用的实时手段的可行性。这项研究将首先确定可测量的组织阻抗变化，这种变化是由电穿孔DNA递送到皮肤引起的。这些变化将用于开发一种反馈算法，该算法将与脉冲发生器和阻抗分析仪一起工作，以控制电穿孔过程中电脉冲的应用。该系统将在一个分泌蛋白的模型中进行测试，以确定与以标准方式应用电穿孔相比，它是否能改善最终的生物反应/表达。如果成功，这项研究将证明一种通过电穿孔将DNA传递到皮肤的改进方式的可行性。研究结果将适用于其他组织。

DESCRIPTION (provided by applicant): Electroporation has evolved, over the past 15 years, as a viable in vivo DNA delivery method/technology. It has been investigated as a delivery method for DNA vaccines, cancer treatment, and the management of metabolic diseases with much success in preclinical studies. These applications have been translated into clinical trials; most of these are still ongoing. The primary complication of this method is controlling the application of direct current pulses so that the maximum or desired level, of expression is achieved in the target tissue. The complication arises from tissue to tissue variation and other factors which can result in under treating or over treating with electric pulses. Currently, no methods exist for controlling the application of pulses while they are being administered. This proposed study is designed to investigate the feasibility of using electrical impedance as a real time means of controlling the application of electroporative pulses. The study will first identify measureable tissue impedance changes that result from electroporative DNA delivery to skin. These changes will be used to develop a feedback algorithm that will work jointly with a pulse generator and impedance analyzer to control the application of electric pulses during the electroporation process. The system will be tested in a model for a secreted protein to determine if it can improve the resulting biological response/expression compared to applying electroporation in the standard manner. If successful, this study will demonstrate the feasibility of an improved manner for delivering DNA by electroporation to the skin. The results will be translatable to other tissues. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to an improved method for delivering DNA based treatments for cancer, metabolic disorders, and immunotherapies. It will also be applicable for delivering DNA based vaccines.