GOALI: Modeling Electroporation-Mediated DNA Delivery

[0108408 . krassowska]该提案为杜克大学和Genetronics公司之间的一个联合项目寻求资金，该项目将专注于电穿孔介导的DNA传递的理论研究。电穿孔是一种基础广泛的技术，其中使用强电击在细胞膜上制造孔，使生物活性分子能够进入细胞内部。尽管电穿孔在生物技术和医学中应用广泛，但它本质上是经验性的，其理论认识落后于实际应用。Genetronics专门开发技术和硬件，利用电穿孔向患者输送救命药物或有益基因，认识到理解电场促进细胞摄取DNA的机制的重要性，并解释了电场对小分子和大分子摄取影响的实验观察到的差异。PI在Genetronics的六个月休假期间对这些问题进行了调查，该项目由NSF GOALI教师工业奖（be - 9974185,8-1-1999至1-31-2000）资助。这项初步研究表明，现有的用于离子和小分子的模型不能描述像DNA这样的大而高电荷分子的吸收。因此，有必要发展一种专门适用于DNA和类似大分子的理论。

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.