EF Therapeutics, Inc is focused on adding proprietary/patented processes to the standard methods forelectrically mediated DNA delivery. This study is designed to help create a device with ourmanufacturing partner that will be commercially viable for use in the US and eventually the rest of theworld. EF Therapeutics exists because gene therapy is not yet a reality, but it is moving in the correctdirection. One obstacle and general difficulty with gene delivery is that methods for delivering genes invivo have not yet achieved a desired level of reliability and control. In vivo electroporation is a methodfor delivering DNA that has been successful in preclinical studies. These studies have been performedusing the technology for a variety of applications. Collectively, they prove that the physical basis of themethod makes it adaptable to any tissue. These studies paved the way for approximately 130 clinicaltrials that use the technology in vivo. Thus, there are clear research and clinical applications for thisDNA delivery method. But, the method could be improved because it still suffers from lack ofcontrol/reliability. One reason for this is that the characteristics of the electric pulses used to induceDNA 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 beidentical to human tissues. In addition, there is variation from individual to individual. Thus, using thesame electric pulses (or dose of electricity) to deliver DNA to a particular type of tissue is not likely to beoptimal each time the method is used in that tissue type. Unfortunately, this is the current state of theart. A means of customizing/adapting electrical treatment in real-time could circumvent this issue andadd to the efficiency/reliability of the method. Another issue with the state of the art is that in vivoelectroporation affects cell membranes and has traditionally been performed at ambient temperature.Moderately increased temperatures could affect the results as they influence membrane fluidity. Thisgoal proposed is to move a small business named EF Therapeutics one step forward in addressingthese two aforementioned aspects in combination to ultimately improve DNA delivery. The basis forthis study is preliminary data that indicate approximately 10-fold increases in delivery when customizedpulses or moderate temperature increases are used alone. The research plan includes identifying andverifying two key components that will ultimately be used in a commercial/clinical device. The first is asystem to heat and control temperature in target tissue. The second is a means for measuring tissueimpedance in real time during pulsation. Completion of this study will remove an obstacle tocommercialization that is currently in progress.
Public Health Relevance Statement: Project narrative: This study is relevant to public health as the results may lead to improvement of a method for delivering DNA based therapeutics using pulsed electric fields. There are currently a large number of clinical trials in this area. The results of this study are likely to be broadly applicable after adaptation to these developed methods.
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