Small molecule-regulated gene silencing technologies

小分子调控基因沉默技术

• 批准号: 0755053
• 负责人: Yohei Yokobayashi
• 金额: $ 39万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0755053&HistoricalAwards=false
• 关键词: Small; molecule; regulated; gene; silencing

CBET-0755053YokobaysahiIntellectual merit Since its recent discovery, RNA interference (RNAi) has emerged as a powerful tool for biologists to selectively repress expression of virtually any gene of their choice. RNAi has helped researchers to discover novel gene functions and how various genes interact, which are crucial to understanding the molecular basis of many biological processes and diseases. Additionally, numerous academic and industrial groups are intensively developing technologies to use RNAi to treat and cure diseases. Consequently, RNAi is expected to become an important technology for both basic science and applications. The goal of this project is to develop novel technologies to control when and where RNAi is induced by small molecule drugs. Chemically-regulated RNAi enables study of genes that are essential for cell survival or growth, observation of dynamic cellular functions, and increased safety for therapeutic applications. The presently available techniques, however, require coexpression of complex engineered protein(s), which can cause immunogenic complications or toxicity. The Principal Investigator's (PI's) proposed strategies harness the ability of RNA to specifically interact with a variety of compounds to engineer RNA to act as both a chemical sensor and RNAi inducer. The results are genetically small, protein-free, RNA nanomachines which sense specific signal molecules in the cell and decide whether or not to trigger RNAi. Broader impacts Although RNAi has quickly become a routine technique in many academic and industrial laboratories, students, especially undergraduate students, have very little opportunity to learn and practice the important technology. This project will allow a number of Biomedical Engineering students at UC Davis to gain hands-on experience with RNAi through the Senior Design course. The students will, in small groups, design novel chemically regulated RNAi systems, construct plasmid vectors to express them in mammalian cell lines, and study their functions over two academic quarters. Through this project, the students will gain valuable experience with RNAi and various bioengineering techniques in a team-oriented environment. Additionally, the research group will host one or two high school students per summer to engage in laboratory research through UC Davis Young Scholars Program.

自最近发现以来，RNA干扰（RNAi）已成为生物学家选择性抑制几乎任何基因表达的有力工具。RNAi帮助研究人员发现新的基因功能以及各种基因如何相互作用，这对于理解许多生物过程和疾病的分子基础至关重要。此外，许多学术和工业团体正在密集开发使用RNAi治疗和治愈疾病的技术。因此，RNAi有望成为一项重要的基础科学和应用技术。该项目的目标是开发新技术来控制小分子药物诱导RNAi的时间和地点。化学调控的RNAi能够研究细胞存活或生长所必需的基因，观察动态细胞功能，并提高治疗应用的安全性。然而，目前可用的技术需要共表达复杂的工程蛋白，这可能导致免疫原性并发症或毒性。主要研究者（PI）提出的策略利用RNA与各种化合物特异性相互作用的能力来工程化RNA，以充当化学传感器和RNAi诱导剂。结果是遗传上小的，无蛋白质的RNA纳米机器，它可以感知细胞中的特定信号分子，并决定是否触发RNAi。 虽然RNAi已迅速成为许多学术和工业实验室的常规技术，但学生，特别是本科生，很少有机会学习和实践这一重要技术。该项目将允许加州大学戴维斯分校的一些生物医学工程学生通过高级设计课程获得RNAi的实践经验。学生将以小组为单位，设计新型化学调控的RNAi系统，构建质粒载体，在哺乳动物细胞系中表达它们，并在两个学术季度内研究它们的功能。通过这个项目，学生将获得宝贵的经验与RNAi和各种生物工程技术在一个团队为导向的环境。此外，研究小组将通过加州大学戴维斯分校青年学者计划每年夏天接待一到两名高中生从事实验室研究。