GOALI: Modeling Electroporation-Mediated Drug Delivery

9974185 Krassowska这项提案寻求资助杜克大学生物医学工程副教授万达·克拉索夫斯卡博士对Genetronics，Inc.进行为期六个月的长期访问。Genetronics是一家药物输送公司，专门开发利用电穿孔向患者输送救命药物或有益基因的技术和硬件。电穿孔是一种基础广泛的技术，它使用强烈的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的应用相当广泛，但它本质上是经验的，其理论理解落后于实际应用。PI最近开发了一种电穿孔模型，与以前的模型相比，它的数值求解成本非常低。这一功能使其成为研究具有显著空间差异的系统中的电穿孔的理想工具，这一功能几乎在所有实验和临床环境中都会发生。因此，PI访问Genetronics的目的是探索这一模型在电穿孔介导的药物传递领域的潜在实际应用。PI和来自Genetronics的合作研究人员已经确定了该模型的使用可以影响新设备和疗法设计的三个可能领域：(1)脉冲形状、强度、持续时间和频率对孔的产生和活性分子的摄取的作用；(2)在极长、低强度脉冲的电穿孔过程中细胞存活；以及(3)将DNA和药物输送到细胞中的多脉冲方案。PI将负责在公司计算机上实施该模型，并为特定应用定制该模型。工业合作者将通过提供有关电穿孔治疗的目标、制剂的几何形状、电击方案和药物特性的信息来为模型开发做出贡献。基因组科学家还将评估模型复制、解释和预测实验结果的情况，并将为PI提供下一阶段模型开发的反馈。如果通过本申请中提出的合作，该模型将能够预测药物和遗传物质向细胞的转移，它将极大地推进电穿孔介导的药物输送的科学基础。

9974185KrassowskaThis proposal seeks funding for an extended, six month visit by Dr. Wanda Krassowska, an Associate Professor of Biomedical Engineering at Duke University, to Genetronics, Inc. A drug delivery company, Genetronics specializes in developing technology and hardware that uses electroporation to deliver life-saving drugs or beneficial genes to patients. 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. The PI has recently developed a model of electroporation that, in contrast to previous models, is very inexpensive to solve numerically. This feature makes it an ideal tool to study electroporation in systems that exhibit significant spatial variations, a feature occurring in nearly all experimental and clinical settings. Therefore, the objective of the PI's visit to Genetronics is to explore potential practical applications of this model in the area of electroporation-mediated drug delivery.The PI and the co-investigators from Genetronics have identified three possible areas in which the use of the model can impact the design of new devices and therapies: (1) the role of pulse shape, strength, duration, and frequency on pore creation and uptake of active molecules; (2) cell survival during electroporation with very long, low intensity pulses; and (3) multi-pulse protocols for delivery of DNA and drugs into cells.The PI will be responsible for implementing the model on the company computer and customizing it for a particular application. The industrial collaborators will contribute to the model development by supplying information on the objectives of the electroporation treatment, the geometry of the preparation, shock protocols, and drug characteristicsThe Genetronics scientists will also evaluate how well the model reproduces, explains, and predicts experimental results and will provide the PI with the feedback for the next stage of model development. If, as a result of the collaboration proposed in this application, the model will be able to predict the transfer of drugs and genetic material to cells, it will substantially advance the scientific foundations of the electroporation-mediated drug delivery.