Collaborative Research: CDI-Type II: Probing Complex Dynamics of Small Interfering RNA (siRNA) Transfection by Petascale Simulations and Network Analysis

合作研究：CDI-Type II：通过 Petascale 模拟和网络分析探索小干扰 RNA (siRNA) 转染的复杂动力学

• 批准号: 1125317
• 负责人: Priya Vashishta
• 金额: $ 108万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1125317&HistoricalAwards=false
• 关键词: Collaborative; Research; CDI; Type; II

The discovery of RNA interference mediated gene silencing by double-stranded RNA is one of the most exciting recent developments in the biological and biomedical sciences. RNAi utilizes a pathway whereby a double-stranded small interfering RNA (siRNA) targets and destroys complementary mRNA in eukaryotic cells to regulate gene expression. Since its discovery just over a decade ago scientists have investigated the potential use of siRNA-based treatment of many diseases such as cancer, liver cirrhosis, hepatitis B, human papillomavirus, and hypercholesterolemia. In principle, siRNA has much broader therapeutic applications than other types of drugs because siRNA can be synthetically designed to silence any gene via the RNAi machinery. Therefore, the primary challenge for therapeutic applications is efficient and non-toxic delivery of siRNA to cells within tissues of interest. The research goal of this CDI project is to design efficient delivery systems for siRNA via supercomputer simulations. Multimillion-atom simulations are performed to study: (1) the effect of siRNAs on the molecular structure of lipid membranes and how structural changes affect the membrane permeability; (2) molecular mechanisms by which siRNA molecules attached to gold nanoparticles cross the membrane and go into a cell; and (3) delivery of siRNAs encapsulated in liposomes by ultrasound. Computational technologies will be used to enable automated design of efficient siRNA delivery systems. This project is promoting scholastic and professional excellence among students. A dual-degree program has been established which gives students the opportunity to obtain a Ph.D. in the physical sciences or an engineering discipline and an M.S. in computer science with specialization in high performance computing and simulations. This research team will also organize computational science workshops for undergraduate students and faculty mentors from Historically Black Colleges and Universities and Minority Serving Institutions.

双链RNA发现RNA干扰介导的基因沉默是生物学和生物医学科学中最令人兴奋的发展之一。 RNAi利用了一条途径，通过该途径，双链小干扰RNA（siRNA）靶标并破坏真核细胞中的互补mRNA来调节基因表达。自从十多年前的发现以来，科学家已经研究了基于siRNA的许多疾病的治疗方法，例如癌症，肝硬化，乙型肝炎，人乳头瘤病毒和高胆固醇血症。原则上，siRNA比其他类型的药物具有更广泛的治疗应用，因为siRNA可以合成以通过RNAi机械沉降任何基因。因此，治疗应用的主要挑战是siRNA向感兴趣的组织内的细胞的无毒递送。该CDI项目的研究目标是通过超级计算机模拟为siRNA设计有效的输送系统。进行了数百万个原子模拟研究：（1）siRNA对脂质膜分子结构的影响，以及结构变化如何影响膜的渗透性； （2）siRNA分子连接到金纳米颗粒的分子机制穿过膜并进入细胞； （3）超声输送在脂质体中封装在脂质体中。计算技术将用于实现有效的siRNA输送系统的自动设计。该项目正在促进学生中的学术和专业卓越。已经建立了一个双度计划，使学生有机会获得博士学位。在物理科学或工程学科和硕士学位中在计算机科学领域具有高性能计算和仿真的专业化。该研究团队还将为历史悠久的黑人学院和大学以及少数民族服务机构的本科生和教师组织组织计算科学研讨会。