RNA INTERFERENCE

RNA干扰

• 批准号: 6990211
• 负责人: Jianzhu Chen
• 金额: $ 35.44万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990211
• 关键词: biomedical facility; biotechnology; high throughput technology; neoplasm /cancer genetics; nucleic acid quantitation /detection; nucleic acid sequence; small interfering RNA

A key aspect of this proposal, embedded in each of the three research projects is the validation of predictions made by computational models of specific cellular programs involve in cancer progression. Those predictions need to be tested in cells and in animals by gain-of-function or loss of-function experiments. RNA interference (RNAi) has emerged as a novel cellular mechanism regulating gene expression at the posttranscriptional level and as a powerful tool to control gene function experimentally There have been several recent advances in the biology and application of RNAi. These include the definition of improved criteria for selecting effective small interfering RNA (siRNA) sequences ; improved methods for delivery of short interfering RNAs (siRNAs) or expression of short hairpin RNAs (shRNAs), which in turn generate siRNAs leading to stable silencing of genes in mammalian cells, tissues, and animals using retroviral expression systems. Both focused and high-throughput screening projects based on RNAi have been initiated to search for genes involved in basic biological processes, as well as in complex pathological conditions associated with cancer. The ICBP RNAi resource will develop new siRNA/shRNA delivery technologies and will provide support to the participants in this program that plan to use RNAi technologies in their research. The specific aims of the RNAi resource facility are to: 1. Generate and distribute a set of functionally validated siRNAs and shRNAs that are able to silence genes of interest to the ICBP. 2. Develop and improve selection criteria for functional siRNA sequences. 3. Develop new approaches to achieve constitutive, regulated, or tissue-specific delivery of siRNAs and expression of shRNAs. 4. Provide technical and scientific advice to ICBP investigators on how to use RNAi technologies.

这项提议的一个关键方面，嵌入了三个研究项目中的每一个，是对参与癌症进展的特定细胞程序的计算模型所做出的预测的验证。这些预测需要通过功能获得或功能丧失实验在细胞和动物身上进行验证。 RNA干扰(RNAi)是一种在转录后水平调控基因表达的新的细胞机制，是实验上控制基因功能的有力工具，近年来RNAi的生物学和应用研究取得了一些进展。这些措施包括改进选择有效小干扰RNA(SiRNA)序列的标准的定义；改进传递短干扰RNA(SiRNAs)或表达短发夹状RNA(ShRNAs)的方法，后者进而产生siRNAs，从而利用逆转录病毒表达系统稳定地沉默哺乳动物细胞、组织和动物中的基因。基于RNAi的重点和高通量筛查项目已经启动，以寻找参与基本生物学过程以及与癌症相关的复杂病理条件的基因。ICBP RNAi资源将开发新的siRNA/shRNA传递技术，并将为计划在他们的研究中使用RNAi技术的这一计划的参与者提供支持。 RNAi资源设施的具体目标是： 1.产生和分发一组功能有效的siRNAs和shRNAs，这些siRNAs和shRNAs能够沉默ICBP关注的基因。 2.发展和完善功能性siRNA序列的筛选标准。 3.开发新的方法来实现结构性、受调控的或组织特异性的siRNAs递送和shRNAs的表达。 4.就如何使用RNAi技术向ICBP调查人员提供技术和科学建议。