CCR RNAi Initiative: Overview

CCR RNAi 计划：概述

• 批准号: 7338740
• 负责人: natasha caplen
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/7338740
• 关键词: CCR; RNAi; Initiative; Overview

The Gene Silencing Section, (GSS) Genetics Branch, aims to be a group with specific expertise within CCR for the study and application of RNAi in mammalian cells. The scientific and clinical developments in the field of RNAi are rapidly impacting our understanding of the role of RNA silencing mechanisms on the control of normal and disease related gene expression, including cancer. Further, technological developments utilizing the RNAi mechanism have been developed for the analysis of gene function and the development of new model systems. More recently RNAi based analysis has been used for improved understanding of drug: target interactions and target identification, and these strategies are now being scaled to enable large scale screening, potentially up to whole genome. In addition to our project based research (see other project reports) we have played an extensive role in assisting and training CCR investigators in the use of RNAi for gene function analysis including, though not limited to, the training of Investigators and Post Doctoral Fellows in different aspects of RNAi analysis technologies, the sharing of protocols and RNAi characterization data (see below), as well as direct collaboration. To develop our first large scale RNAi effector resource Dr. Caplen, the GSS section head, developed a research collaboration agreement (RCA #2-18668-05, AKA MTA 18668) between the Gene Silencing Section, OSTP, OD, CCR (as of June 2006 GSS became aligned with the Genetics Branch, CCR) and Qiagen Inc. We have enabled CCR investigators to access confidential RNAi analysis data for 100 human genes, and this has resulted in the execution of over 30 intramural Material Transfer Agreements and the transfer of appropriate information to CCR investigators. As a direct result of data gathered as part of the initiative, plus additional collaborative work by Dr. John Weinstein's group, LMP, CCR) a patent application has been filed (full details are described in project Z01 BC 010613). Further, work with LBC, CCR (Drs. Gottesman, Ludwig and Szakacs) (detailed in project Z01 BC 010609) has enabled validation of a relationship between the expression of MDR1 (ABCB1) and a novel drug (NSC77360). This work has contributed to this small compound being further studied as part of a joint CCR/NCI-DTP drug development initiative. Dr. Caplen, the GSS section head has also been involved with two additional collaborative projects published in 2006. One study investigated the alternative delivery methods of synthetic siRNA and the other examined in vivo application of synthetic siRNAs to the respiratory system. These studies illustrate the sections commitment to stay aware of different strategies for delivery of RNAi effectors and we have assisted a number of CCR investigators considering or actually conducting, in vivo RNAi analysis. We have also been actively pursuing the development of even larger scale RNAi resources that can be used for high-throughput RNAi screening. Our resources by end FY06 will include, the library of 900 siRNAs (450 human genes) developed under a RCA with Qiagen Inc. and detailed above, a commercial siRNA library sufficient for 900 data points/siRNA and corresponding to 7,000 human genes representing the "druggable genome" and a replicated retroviral based shRNA whole human genome RNAi library. The aim of obtaining these resources and the expertise to use them has been to develop a collaborative program that CCR investigators can access for larger scale RNAi analysis than they would be able to perform within their own laboratories. Further, the recent placement of GSS within the Genetics Branch, CCR now gives us a unique opportunity to combine the RNAi expertise of GSS with the genome-wide analysis expertise of Dr. Meltzer's group and other groups within the Genetics Branch.

基因沉默组，（GSS）遗传学分支，旨在成为CCR内的一个具有特定专业知识的小组，用于哺乳动物细胞中RNAi的研究和应用。RNAi领域的科学和临床发展正在迅速影响我们对RNA沉默机制在控制正常和疾病相关基因表达（包括癌症）中的作用的理解。此外，已经开发了利用RNAi机制的技术开发，用于分析基因功能和开发新的模型系统。最近，基于RNAi的分析已被用于改善对药物：靶标相互作用和靶标鉴定的理解，并且这些策略现在被缩放以实现大规模筛选，可能高达整个基因组。除了我们基于项目的研究（见其他项目报告），我们还在协助和培训CCR研究人员使用RNAi进行基因功能分析方面发挥了广泛的作用，包括但不限于在RNAi分析技术的不同方面培训研究人员和博士后研究员，共享协议和RNAi表征数据（见下文），以及直接合作。为了开发我们的第一个大规模RNAi效应物资源，GSS部门负责人Caplen博士在基因沉默部门、OSTP、OD、CCR（截至2006年6月，GSS与CCR遗传学分支结盟）和Qiagen Inc.之间制定了研究合作协议（RCA #2-18668-05，AKA MTA 18668）。我们使CCR研究人员能够访问100个人类基因的机密RNAi分析数据，这导致了30多个内部材料转让协议的执行，并将适当的信息转移给CCR研究人员。作为该计划的一部分收集的数据的直接结果，加上John Weinstein博士的团队，LMP，CCR的额外合作工作，已经提交了专利申请（完整细节在项目Z 01 BC 010613中描述）。此外，与LBC、CCR（Drs. Gottesman、Ludwig和Szakacs）的合作（详见项目Z 01 BC 010609）已能够验证MDR 1（ABCB 1）表达与新药（NSC 77360）之间的关系。这项工作有助于进一步研究这种小化合物，作为CCR/NCI-DTP联合药物开发计划的一部分。Caplen博士，GSS部门负责人还参与了2006年出版的另外两个合作项目。一项研究调查了合成siRNA的替代递送方法，另一项研究调查了合成siRNA在呼吸系统中的体内应用。这些研究说明了本节致力于了解RNAi效应物递送的不同策略，并且我们已经帮助许多CCR研究人员考虑或实际进行体内RNAi分析。我们也一直在积极寻求更大规模的RNAi资源的开发，可用于高通量RNAi筛选。到2006财政年度结束时，我们的资源将包括在与Qiagen Inc.的RCA下开发的900个siRNA（450个人类基因）的文库。和上文详述的，足以900个数据点/siRNA并对应于代表“可药物化基因组”的7，000个人类基因的商业siRNA文库和复制的基于逆转录病毒的shRNA全人类基因组RNAi文库。获得这些资源和使用它们的专业知识的目的是开发一个合作计划，CCR研究人员可以访问比他们自己的实验室更大规模的RNAi分析。此外，最近GSS在CCR遗传学分支中的位置现在为我们提供了一个独特的机会，将GSS的RNAi专业知识与Meltzer博士小组和遗传学分支中其他小组的全基因组分析专业知识相结合。