Trans-NIH RNAi Facility (TNRF)

跨 NIH RNAi 设施 (TNRF)

• 批准号: 9205806
• 负责人: Anton Simeonov
• 金额: $ 47.5万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9205806
• 关键词: Trans; NIH; RNAi; Facility; TNRF

Small interfering RNA (siRNA) molecules are pieces of RNA that block the activity of genes through a natural process called RNA interference (RNAi). RNAi has emerged as a powerful tool used in thousands of labs worldwide to understand gene function. By blocking or modulating a genes function, RNAi can tell us about the role of any gene in maintaining health or causing disease, an invaluable step in identifying potential drug targets. In tests called genome-wide RNAi screens, scientists use automation to introduce siRNAs into human cells to block the activity of each gene, one at a time. This process can produce a complete list of all genes involved in a particular biological function or disease process. Scientists also can use these techniques to understand what roles genes play in drug effectiveness. RNAis potential usefulness has been limited by the lack of expertise to perform genome-wide RNAi screens, the lack of methodologies that can properly interpret these experiments and the absence of comprehensive RNAi data in public databases for researchers to reference. To address these problems, NCATS operates a state-of-the-art RNAi screening facility, and NCATS staff assists NIH intramural investigators with all stages of project planning and execution. The initiative provides public access to RNAi data generated from these experiments through the National Library of Medicines PubChem database. In addition, siRNA sequence information is available from private-sector biotechnology partners. For instance, researchers can access Life Technologies Silencer Select siRNA library, which includes 65,000 siRNA sequences that target more than 20,000 human genes. The RNAi high-throughput screening facility, administered by NCATS Division of Pre-Clinical Innovation staff, offers a robotic platform with integrated, automated devices for conducting all aspects of screening assays (tests), including manipulating chemicals and cells, reading the results and imaging the cells. Offline (non-robotic) devices can perform smaller-scale work from assay optimization through medium-scale screening. Investigators have the option of using several different siRNA libraries and other small molecules involved in RNAi. For data analysis, the facility offers powerful computational tools. In addition to enabling collaborations on specific projects, RNAi facility staff work to develop methods that advance the science of RNAi screening and informatics and pursue new technologies for exploring gene function. Currently, NCATS scientists are working on developing a platform that offers complementary high-throughput genomic technologies to advance the field of functional genomics. The goal is to speed scientific discoveries in all disease areas. Project areas include cancer (drug enhancer/resistance screens, development of 3-D metastasis screens, molecular targets in cancer and cancer-related pathways), infectious diseases (viral infection and replication such as HIV, Ebola virus and Hepatitis C virus), fundamental cell biology (DNA replication and reprogramming/differentiation), and other disease-related phenotypes (Parkinsons disease, diabetes and fragile X syndrome).

小干扰RNA（siRNA）分子是通过称为RNA干扰（RNAi）的自然过程阻断基因活性的RNA片段。RNAi已成为全球数千个实验室用于了解基因功能的强大工具。通过阻断或调节基因功能，RNAi可以告诉我们任何基因在维持健康或引起疾病中的作用，这是确定潜在药物靶点的宝贵步骤。在称为全基因组RNAi筛选的测试中，科学家使用自动化将siRNA引入人类细胞中，以一次一个地阻断每个基因的活性。这个过程可以产生一个完整的列表，列出所有参与特定生物功能或疾病过程的基因。科学家们也可以利用这些技术来了解基因在药物有效性中扮演的角色。 由于缺乏进行全基因组RNAi筛选的专业知识，缺乏可以正确解释这些实验的方法，以及公共数据库中缺乏可供研究人员参考的全面RNAi数据，限制了RNAi的潜在用途。为了解决这些问题，NCATS运营着最先进的RNAi筛选设施，NCATS工作人员协助NIH内部研究人员进行项目规划和执行的所有阶段。该计划通过国家医学图书馆PubChem数据库向公众提供从这些实验中产生的RNAi数据。此外，siRNA序列信息可从私营部门生物技术合作伙伴处获得。例如，研究人员可以访问Life Technologies Silencer Select siRNA文库，其中包括65，000个siRNA序列，靶向超过20，000个人类基因。RNAi高通量筛选设施由NCATS临床前创新部门的工作人员管理，提供了一个机器人平台，该平台具有集成的自动化设备，用于进行筛选测定（测试）的所有方面，包括操作化学品和细胞，阅读结果和对细胞进行成像。离线（非机器人）设备可以执行从分析优化到中等规模筛选的小规模工作。研究人员可以选择使用几种不同的siRNA文库和其他参与RNAi的小分子。对于数据分析，该设施提供了强大的计算工具。 除了在特定项目上进行合作外，RNAi设施的工作人员还致力于开发推进RNAi筛选和信息学科学的方法，并寻求探索基因功能的新技术。目前，NCATS的科学家们正在开发一个平台，提供互补的高通量基因组技术，以推进功能基因组学领域。目标是加速所有疾病领域的科学发现。项目领域包括癌症（药物增强剂/耐药性筛选，3-D转移筛选的开发，癌症和癌症相关途径的分子靶点），传染病（病毒感染和复制，如HIV，埃博拉病毒和丙型肝炎病毒），基础细胞生物学（DNA复制和重编程/分化）以及其他疾病相关表型（帕金森病，糖尿病和脆性X综合征）。