siRNA for Drug Target Validation in Mammalian Cells

用于哺乳动物细胞中药物靶标验证的 siRNA

• 批准号: 6552152
• 负责人: David Lawrence Lewis
• 金额: $ 11.04万
• 依托单位: MIRUS BIO CORPORATION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6552152
• 关键词: RNA; cytokine; drug delivery systems; drug discovery /isolation; drug metabolism; gene expression; gene targeting; laboratory mouse; reporter genes; technology /technique development

DESCRIPTION (provided by applicant): The tremendous progress made in the medical sciences and genomics has given rise to a plethora of new candidate drug targets. However, it is becoming increasingly apparent that a major bottleneck in the drug discovery process is not always drug design per se, but rather identification of which of the candidate targets most contributes to the particular diseased state. Recently, a revolutionary new method termed RNA interference (RNAi) has been shown to be highly effective at inhibiting the expression of specific target genes in mammalian cells in vitro. The overall objective of the studies proposed in this SBIR Fast Track grant application is to develop the use of RNAi for the purposes of drug target validation in mammalian cells in vitro and in vivo. In Phase I studies, we will develop reagents for delivery of siRNA and explore the utility of siRNA for inhibiting reporter gene expression in mammalian cells in vitro. In Phase II studies, we will apply RNAi technology to components of the insulin signal transduction pathway as a proof-of-principle test. We will also explore the use of RNAi technology to inhibit expression of genes in small animals in order to validate drug targets in vivo.

描述(申请人提供)：医学科学和基因组学取得的巨大进步催生了过多的新候选药物靶点。然而，越来越明显的是，药物发现过程中的一个主要瓶颈并不总是药物设计本身，而是确定哪些候选目标对特定的疾病状态最有贡献。 最近，一种名为RNA干扰(RNAi)的革命性新方法被证明在体外高效地抑制哺乳动物细胞中特定靶基因的表达。在这项SBIR Fast Track补助金申请中提出的研究的总体目标是开发RNAi在哺乳动物细胞体外和体内药物靶标验证方面的用途。在第一阶段的研究中，我们将开发siRNA递送试剂，并探索siRNA在体外抑制哺乳动物细胞报告基因表达的作用。在第二阶段的研究中，我们将把RNAi技术应用于胰岛素信号转导通路的组件，作为原理验证测试。我们还将探索使用RNAi技术来抑制小动物的基因表达，以验证体内的药物靶点。