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Model of Creation and Evolution of Stable Electropores for DNA Delivery

Kyle C. Smith ^*, John C. Neu ^*  and Wanda Krassowska ^*

^* Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708; and Department of Mathematics, University of California, Berkeley, California 94720

Correspondence: Address reprint requests to Wanda Krassowska, Tel.: 919-660-5105; Fax: 919-660-5405; E-mail: wanda.krassowska{at}duke.edu.

Electroporation, in which electric pulses create transient pores in the cell membrane, is becoming an important technique for gene therapy. To enable entry of supercoiled DNA into cells, the pores should have sufficiently large radii (>10 nm), remain open long enough for the DNA chain to enter the cell (milliseconds), and should not cause membrane rupture. This study presents a model that can predict such macropores. The distinctive features of this model are the coupling of individual pores through membrane tension and the electrical force on the pores, which is applicable to pores of any size. The model is used to explore the process of pore creation and evolution and to determine the number and size of pores as a function of the pulse magnitude and duration. Next, our electroporation model is combined with a heuristic model of DNA uptake and used to predict the dependence of DNA uptake on pulsing parameters. Finally, the model is used to examine the mechanism of a two-pulse protocol, which was proposed specifically for gene delivery. The comparison between experimental results and the model suggests that this model is well-suited for the investigation of electroporation-mediated DNA delivery.

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