Identification of impedance measurement devices, heating hardware, and operating parameters to augment instrumentation for a commercial in vivo electroporation system

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PROJECT SUMMARY / ABSTRACT: EF Therapeutics, Inc is focused on adding proprietary/patented processes to the standard methods for electrically mediated DNA delivery. This study is designed to help create a device with our manufacturing partner that will be commercially viable for use in the US and eventually the rest of the world. EF Therapeutics exists because gene therapy is not yet a reality, but it is moving in the correct direction. One obstacle and general difficulty with gene delivery is that methods for delivering genes in vivo have not yet achieved a desired level of reliability and control. In vivo electroporation is a method for delivering DNA that has been successful in preclinical studies. These studies have been performed using the technology for a variety of applications. Collectively, they prove that the physical basis of the method makes it adaptable to any tissue. These studies paved the way for approximately 130 clinical trials that use the technology in vivo. Thus, there are clear research and clinical applications for this DNA delivery method. But, the method could be improved because it still suffers from lack of control/reliability. One reason for this is that the characteristics of the electric pulses used to induce DNA uptake are normally fixed for a particular tissue type based upon optimization in animal models. These may have little translatability to analogous tissues in clinical settings as models may not be identical to human tissues. In addition, there is variation from individual to individual. Thus, using the same electric pulses (or dose of electricity) to deliver DNA to a particular type of tissue is not likely to be optimal each time the method is used in that tissue type. Unfortunately, this is the current state of the art. A means of customizing/adapting electrical treatment in real-time could circumvent this issue and add to the efficiency/reliability of the method. Another issue with the state of the art is that in vivo electroporation affects cell membranes and has traditionally been performed at ambient temperature. Moderately increased temperatures could affect the results as they influence membrane fluidity. This goal proposed is to move a small business named EF Therapeutics one step forward in addressing these two aforementioned aspects in combination to ultimately improve DNA delivery. The basis for this study is preliminary data that indicate approximately 10-fold increases in delivery when customized pulses or moderate temperature increases are used alone. The research plan includes identifying and verifying two key components that will ultimately be used in a commercial/clinical device. The first is a system to heat and control temperature in target tissue. The second is a means for measuring tissue impedance in real time during pulsation. Completion of this study will remove an obstacle to commercialization that is currently in progress.