CAREER:Self-Assembled Biodegradable Conjugated Polymers for RNA Interference

职业：用于 RNA 干扰的自组装可生物降解共轭聚合物

• 批准号: 1352317
• 负责人: Joong Ho Moon
• 金额: $ 48.95万
• 依托单位: Florida International University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352317&HistoricalAwards=false
• 关键词: CAREER; Self; Assembled; Biodegradable; Conjugated

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.

非技术摘要这项由材料研究部生物材料计划支持的职业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输送效率。将核酸(即DNA和RNA)分子安全高效地运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复合体的细胞进入/定位，PI有望有效地控制基因功能，超过现有载体目前的性能水平。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。科学界的早期研究经验和参与，以及留住现有的少数族裔本科生攻读学位课程，被认为是提高科学、技术、工程和数学(STEM)少数族裔人数的有效途径。该项目的教育目标是通过有重点的外展计划增加科学和工程领域的少数族裔人数。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进入研究生院，以及为本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兴奋。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。该职业项目的目标是：1)建立一个跨学科的生物材料研究计划，促进我们对聚合物基因/药物输送材料结构-功能关系的理解；2)开发创新的教育方法，通过外联计划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，但载体的低传递效率和毒性阻碍了基于RNAi的治疗的进一步突破。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-生物功能关系。调节和控制载体的化学结构将有助于深入了解载体的表面性质如何影响细胞进入路径和局域化。最后，CPS的生物降解性允许通过细胞内拆分有效地释放RNA。利用具有优良光物理性质的CP对递送事件的可视化和靶细胞的标记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外展计划，与大量当地高中、本科生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接待4-6所高中(每所学校40名学生)，为代表不足的学生提供大学水平的研究体验。