CAREER:Self-Assembled Biodegradable Conjugated Polymers for RNA Interference

非技术摘要由材料研究部生物材料项目支持的这项职业奖的科学目标是通过系统研究结构-功能关系来提高合成载体的递送效率。 核酸的安全和有效递送（即，DNA和RNA）分子靶向组织和细胞对许多疾病具有很高的治疗潜力，因为这些分子可以特异性地阻断与疾病相关的基因的功能。通过优化化学和物理性质并了解共轭聚合物/RNA复合物的细胞进入/定位，PI有望有效控制基因功能，超过现有载体的当前性能水平。本项目所获得的知识将对设计和制造各种合成基因和药物递送系统产生更广泛的影响。早期的研究经验和参与科学界和保留现有的少数民族本科生学位课程被认为是有效的方法，以提高少数民族在科学，技术，工程和数学（STEM）的数量。该项目的教育目标是通过有重点的外展方案，增加少数民族在科学和工程领域的人数。通过将研究成果融入课堂，以激励学生追求更高的学位，为本科院校（UIs）的学生提供研究/职业发展研讨会，以鼓励学生进入研究生院，并为当地高中生提供研究机会，以提供早期的研究经验和参与科学界，PI将通过教学和传播培养研究的兴奋。通过该项目建立的关系将有助于支持佛罗里达东南部的科学和工程培训和教育。技术摘要该CAREER项目的目标是1）建立一个跨学科的生物材料研究计划，以促进我们对聚合基因/药物递送材料的结构-功能关系的理解，2）发展创新的教育方法，通过推广方案增加少数民族学生在科学和工程方面的人数。尽管RNA干扰（RNAi）技术令人兴奋，但载体的低递送效率和毒性阻碍了基于RNAi的疗法的进一步突破。该项目允许PI通过使用荧光半导体共轭聚合物（CP）在细胞水平上系统地研究载体结构与生物功能的关系。调节和控制载体的化学结构将导致深入了解载体的表面性质如何影响细胞进入途径和定位。最后，CP的生物降解性允许通过细胞内解包有效释放RNA。递送事件的可视化和用具有优异生物物理性质的CP标记靶细胞也有利于开发多功能生物材料。该项目将允许PI通过推出包括大学体验计划在内的推广计划，与当地大量高中，本科和研究生分享研究经验的兴奋。PI和化学俱乐部成员每年将举办4-6所高中（每所学校40名学生），为代表性不足的学生提供大学水平的研究经验。

Non-Technical AbstractThe scientific goal of this CAREER Award supported by the Biomaterials program in the Division of Materials Research is to improve the delivery efficiency of synthetic carriers through systematic investigations of the structure-function relationships. Safe and efficient delivery of nucleic acid (i.e., DNA and RNA) molecules to target tissues and cells has high therapeutic potentials against many diseases, because the molecules can specifically block the functions of genes associated with diseases. By optimizing chemical and physical properties and understanding cellular entry/localization of conjugated polymer/RNA complexes, the PI expects to control gene functions efficiently, exceeding current performance levels of the existing carriers. The knowledge obtained from this project will have broader impact on designing and fabricating various synthetic gene and drug delivery systems. Early research experiences and engagements in scientific communities and retaining existing minority undergraduate students in degree programs are recognized as efficient ways to improve the number of minorities in science, technology, engineering, and mathematics (STEM). The education goal of this project is to increase the number of minorities in science and engineering through focused outreach programs. By integrating research results into classes to motivate students to pursue higher degree, offering research/career development seminars designed for students at undergraduate institutes (UIs) to encourage students to go to graduate school, and offering research opportunities to local high school students to provide early research experiences and engagement in scientific communities, the PI will cultivate the excitement of research through teaching and dissemination. The relationships built through the proposed project will help support science and engineering training and education in Southeast Florida.Technical AbstractThe goals of this CAREER project are 1) to establish an interdisciplinary biomaterials research program that advances our understanding on the structure-function relationships of polymeric gene/drug delivery materials and 2) to develop innovative educational methods to increase the number of minority students in science and engineering through outreach programs. Despite the excitement regarding RNA interference (RNAi) technology, poor delivery efficiency and toxicity of carriers hinders further breakthroughs in RNAi-based therapeutics. This project allows the PI to systematically investigate the carrier structure-biological function relationships at the cellular level by using fluorescent semiconducting conjugated polymers (CPs). Modulating and controlling the chemical structures of the carriers will lead to in-depth understanding of how the surface properties of the carriers influence the cellular entry pathways and localizations. Finally, biodegradability of CPs allows efficient release of RNA through intracellular unpacking. Visualization of the delivery event and labeling of target cells with CPs having excellent photophysical properties are also beneficial for developing multifunctional biomaterials. The project will allow the PI to share the excitement of the research experience with a significant number of local high school, undergraduate, and graduate students by launching outreach programs including the University Experience Program. The PI and Chemistry Club members will host 4-6 high schools (40 students per school) per year to offer a college-level research experience to underrepresented students.