Gene therapy is not yet a reality, but it is moving in the correct direction. One obstacle and generalization 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 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 over 100 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 Diversity Supplement is to provide research training to a very well qualified Hispanic engineer while addressing these two aforementioned aspects in combination to ultimately improve delivery to tissues such as cutaneous tumors and muscle. 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 designing a custom electrode array with penetrating electrodes (needles) that can heat tissues in a controlled manner. It also involves designing and building a device to use with this electrode to apply fast electric pulses to tumors and muscle as well as monitor impedance as a control parameter to customize pulsing in real time during treatment. The mentee will use the design, construction, and testing of this instrument system as his dissertation under the guidance of two experienced mentors. This guided project will include conference presentations, multiple interactions with other researchers at conferences, exposure to top researchers in the field at the international level, and grant writing mentorship.
This study is relevant to public health as it will improve diversity within the group of scientists that perform biomedical research. Furthermore, the results may lead to an improved method for delivering DNA-based therapeutics. The results of this study are likely to be broadly applicable, after adaptation, to treat or prevent disease.
