CAREER:Self-Assembled Biodegradable Conjugated Polymers for RNA Interference

由材料研究部生物材料项目支持的CAREER奖的科学目标是通过对结构-功能关系的系统研究来提高合成载体的递送效率。安全有效地将核酸（即DNA和RNA）分子递送到靶组织和细胞中，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以及了解共轭聚合物/RNA复合物的细胞进入/定位，PI期望有效地控制基因功能，超越现有载体的当前性能水平。从该项目中获得的知识将对设计和制造各种合成基因和药物输送系统产生更广泛的影响。早期的研究经验和在科学界的参与，以及在学位课程中保留现有的少数民族本科生，被认为是提高科学、技术、工程和数学（STEM）领域少数民族人数的有效途径。该项目的教育目标是通过有针对性的外展项目增加科学和工程领域少数民族的人数。通过将研究成果融入课堂以激励学生追求更高的学位，为本科生提供研究/职业发展研讨会以鼓励学生去读研究生，并为当地高中生提供研究机会，以提供早期研究经验和参与科学社区，PI将通过教学和传播培养研究的激情。通过拟议的项目建立的关系将有助于支持佛罗里达州东南部的科学和工程培训和教育。本项目的目标是：1)建立一个跨学科的生物材料研究项目，促进我们对高分子基因/药物传递材料的结构-功能关系的理解；2)开发创新的教育方法，通过外展项目增加理工科少数民族学生的数量。尽管RNA干扰（RNAi）技术令人兴奋，但较差的递送效率和载体的毒性阻碍了基于RNAi的治疗方法的进一步突破。该项目允许PI通过使用荧光半导体共轭聚合物（CPs）在细胞水平上系统地研究载体结构-生物功能关系。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，CPs的可生物降解性允许RNA通过细胞内解包有效释放。利用具有优异光物理性质的CPs对靶细胞进行传递过程的可视化和标记也有利于开发多功能生物材料。该项目将通过推出包括大学体验计划在内的外展项目，让PI与大量当地高中生、本科生和研究生分享研究经历的兴奋。PI和化学俱乐部成员每年将接待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.