Modulation of Gene Expression Through RNAi

核心B通过提供最先进的RNAi工具来支持该计划中的每个项目。短 发夹RNA（shRNA）是在该计划的支持下以及Core的持续创新下开发的 B和项目研究人员帮助制造了这些极其强大的生物工具。在过去 在资助期间，核心设计了快速工程小鼠携带调控shRNA表达的方法 盒，设计了以多重方式功能验证shRNAs的策略，并创建了第三个 产生对应于人和小鼠中注释的蛋白质编码基因的RNAi文库。期间 在即将到来的请求支持期间，核心建议通过五个方面帮助计划调查人员， 一般目标。首先，该计划将继续提供最先进的RNAi工具， 单基因敲除或用于进行合并的RNAi筛选。第二，核心将与 研究人员进行“传感器测定”，以识别针对感兴趣基因的最佳shRNAs工具。第三、 核心将针对程序感兴趣的基因组产生定制的RNAi文库， investigators.第四，核心将产生携带受调控的RNAi盒的小鼠，并帮助研究人员 将这些与其他所需的遗传病变结合起来。最后，核心将继续努力改善RNAi 技术，并使这些创新提供给该计划和整个社区。

Core B supports every project within the Program by providing access to state-of-the-art RNAi tools. Short hairpin RNAs (shRNAs) were developed with the support of this program, and ongoing innovations by Core B and Program investigators have helped to make these extremely powerful biological tools. During the past funding period, the Core devised methods to rapidly engineer mice carrying regulated shRNA expression cassettes, devised strategies for functionally validating shRNAs in a multiplexed fashion, and created a third generation of RNAi libraries corresponding to annotated protein coding genes in humans and mice. During the upcoming period of requested support, the core proposes to aid Program investigators through five general aims. First, the program will continue to provide access to state-of-the-art RNAi tools for analyzing either single gene knockdowns or for performing pooled RNAi screens. Second, the Core will work with investigators to operate the "sensor assay" to identify optimal shRNAs tools against genes of interest. Third, the core will produce custom RNAi libraries against sets of genes that are of interest to Program investigators. Fourth, the Core will produce mice carrying regulated RNAi cassettes and aid investigators in combining these with other desired genetic lesions. Finally, the Core will carry on its efforts to improve RNAi technologies and make those innovations available to the Program and to the community at large.