Impedance Changes as an Indicator of Successful Skin Electroporative DNA delivery

描述(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输送方法/技术。作为DNA疫苗、癌症治疗和代谢性疾病治疗的一种递送方法，它已被研究，并在临床前研究中取得了很大成功。这些申请已经转化为临床试验；其中大多数仍在进行中。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所需的表达水平。并发症产生于组织到组织的变异和其他因素，这些因素可能导致电脉冲治疗不足或过度治疗。目前，不存在用于在给药时控制脉冲施加的方法。这项拟议的研究旨在调查使用电阻抗作为控制电穿孔脉冲施加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，这些变化是由电穿孔DNA传递到皮肤造成的。这些变化将被用来开发一种反馈算法，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。该系统将在分泌蛋白质的模型中进行测试，以确定与以标准方式应用电穿孔相比，它是否可以改善所产生的生物反应/表达。如果成功，这项研究将证明一种通过电穿孔将DNA输送到皮肤的改进方式的可行性。这一结果将可用于其他组织。 公共卫生相关性：这项研究与公共健康相关，因为其结果可能导致一种改进的方法，用于提供基于DNA的癌症、代谢障碍和免疫治疗。它也将适用于交付基于DNA的疫苗。

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.