Modeling Electroporation-Mediated DNA Delivery

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0401757KrassowskaThis renewal proposal seeks funding to complete the work on modeling electroporation that wasstarted under the NSF grants BES-9974185 and BES-0108408. Electroporation is a technique in which strong electrical shocks are used to create pores in the cell membrane that enable biologically active molecules to enter the cell interior. Despite numerous applications of electroporation to drug and DNA delivery, the theory underlying this process is still lacking. Previous research funded by the NSF allowed the PI and her team to make significant progress in this area, by development of a model that gives good qualitative, and sometimes even quantitative, agreement with experiments. However, consistent quantitative agreement cannot be reached without modeling both temporal and spatial aspects of electroporation, which is the focus of the research proposed in this application. The goals of this project are:(1) Develop an asymptotic simplification of the existing model of pore creation and evolution, which would give results equivalent to the existing model without its computational expense.(2) Develop a model of electric field-driven DNA flux through macropores that could be used forlinear, circular, or supercoiled DNA. (3) Synthesize the pore creation and evolution model and the DNA flux model in the context of two prototypical spatially extended systems, a single cell and a one-dimensional fiber. These models will provide the proof of concept that a comprehensive and realistic model of electroporation in cells and tissues is feasible, and they will lay the foundation for modeling clinical procedures involving in-vivo electroporation.An interdisciplinary research team consisting of Dr. Wanda will perform the researchKrassowska (PI, Biomedical Eng., Duke University), Dr. John Neu (Mathematics, UC Berkeley),a graduate research assistant, and undergraduate students. The model will be evaluated yearlyby the R&D scientists from Genetronics, Inc., a company that specializes in developing technology and hardware for medical applications of electroporation.