CAREER: Synthetic Design and Biological Study of Novel Polymeric DNA Delivery Vehicles

职业：新型聚合 DNA 递送载体的合成设计和生物学研究

• 批准号: 0449774
• 负责人: Theresa Reineke
• 金额: --
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0449774&HistoricalAwards=false
• 关键词: CAREER; Synthetic; Design; Biological; Study

With the support of the Organic and Macromolecular Chemistry Program in the Chemistry Division and the Biomolecular Systems Program in the Molecular and Cellular Biosciences Division, Professor Theresa Reineke of the University of Cincinnati will identify how the presence of hydroxyl groups, the number of amine centers, the density of the cationic charge centers, the charge center type, and the geometry of polymeric materials promote effective nucleic acid binding, and she will determine how the chemical and structural properties detailed above affect cytotoxicity, intracellular delivery, and gene expression within living cells. The development of efficient and nontoxic nucleic acid delivery vehicles has become one of the most significant and fundamental problems facing research fields involving gene function, cellular signaling, gene therapy, genetic vaccines, and plant biotechnology. Due to the dangers associated with virus-based delivery systems, polymeric vectors now show great promise. However, problems with toxicity, low delivery efficiency, and a lack of insight into the polymer structure-biological property relationships have hampered their use. The goals of the proposal will be accomplished by synthesizing five novel polymer families that vary in the functionalities mentioned above and by studying the polymer-DNA interactions via isothermal titration calorimetry, dynamic light scattering, and zeta potential measurements. Lowry protein, beta-galactosidase, and luciferase gene expression assays will be performed with a variety of cell lines transfected with the new polymers. The Organic and Macromolecular Chemistry Program and the Biomolecular Systems Program in the Molecular and Cellular Biosciences Division supports Professor Theresa Reineke of the University of Cincinnati who will establish and promote interactive mentoring, cooperative learning, and research programs that successfully unite teaching and scholarship. This will be completed through developing a structured mentoring program called Emerging Ethnic Scientists (EES) that incorporates interactive and cooperative learning techniques into a Freshman Chemistry course and mentoring high school and undergraduate students in the process of scientific research. The long-range goals and broader impacts of this work are to formulate a design model that can be utilized by researchers in the field of polymeric gene delivery to develop efficient and nontoxic vectors for specific cell types and applications and impart to students the excitement of performing interdisciplinary research with the goal of increasing the retention of underrepresented groups in the sciences. Students involved in this interdisciplinary program will gain a uniquely broad and in-depth experience in several areas ranging from synthetic chemistry and polymer science to molecular biology.

在化学学部的有机和大分子化学项目以及分子和细胞生物科学部的生物分子系统项目的支持下，辛辛那提大学的Theresa Reineke教授将确定羟基的存在、胺中心的数量、阳离子电荷中心的密度、电荷中心的类型和聚合物材料的几何形状如何促进有效的核酸结合。她将确定上述化学和结构特性如何影响细胞毒性、细胞内传递和活细胞内的基因表达。开发高效、无毒的核酸载体已成为基因功能、细胞信号、基因治疗、基因疫苗和植物生物技术等研究领域面临的最重要和最根本的问题之一。由于与基于病毒的传递系统相关的危险，聚合载体现在显示出很大的希望。然而，毒性、低传递效率以及缺乏对聚合物结构-生物性质关系的了解等问题阻碍了它们的使用。该提案的目标将通过合成上述功能不同的五种新型聚合物家族，并通过等温滴定量热法，动态光散射和zeta电位测量来研究聚合物- dna相互作用来实现。Lowry蛋白、β -半乳糖苷酶和荧光素酶基因表达分析将在多种转染了新聚合物的细胞系中进行。分子和细胞生物科学部的有机和大分子化学项目和生物分子系统项目支持辛辛那提大学的Theresa Reineke教授，她将建立和促进互动指导、合作学习和研究项目，成功地将教学和学术结合起来。这将通过开发一个名为新兴民族科学家（EES）的结构化指导计划来完成，该计划将互动和合作学习技术纳入新生化学课程，并在科学研究过程中指导高中生和本科生。这项工作的长期目标和更广泛的影响是制定一个设计模型，可以被聚合基因传递领域的研究人员利用，为特定细胞类型和应用开发高效无毒的载体，并传授给学生进行跨学科研究的兴奋，目标是增加科学中代表性不足群体的保留。参与这个跨学科项目的学生将在合成化学、聚合物科学和分子生物学等多个领域获得独特而广泛和深入的经验。