GOALI: Modeling Electroporation-Mediated DNA Delivery

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0108408KrassowskaThis proposal seeks funding for a joint project between Duke University and Genetronics, Inc. that will focus on theoretical studies of electroporation-mediated DNA delivery. Electroporation is a broad-based 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. Even though it is used quite extensively in biotechnology and medicine, electroporation is essentially empirical and its theoretical understanding lags behind practical applications. Genetronics, which specializes in developing technology and hardware that uses electroporation to deliver life-saving drugs or beneficial genes to patients, recognizes the importance of understanding the mechanism by which an electric field promotes the uptake of DNA by cells and explaining differences observed experimentally in the effects of electric fields on the uptake of small vs. large molecules. These issues were investigated by the PI during her six month sabbatical at Genetronics, which was funded by the NSF GOALI Faculty in Industry award (BES-9974185, 8-1-1999 to 1-31-2000). This preliminary research revealed that the existing models, developed for ions and small molecules, do not describe the uptake of large and highly charged molecules such as DNA. Therefore, there is a need to develop a theory that would be applicable specifically to DNA and similar macromolecules.