Algorithm and genome-wide database of functional siRNAs

描述(申请人提供)：由于各种全基因组测序和基因表达项目积累了大量数据，迫切需要开发新的生物信息学工具和技术来揭示人类基因组中每个基因的功能。最近基于小干扰RNA(SiRNA)的基因敲除技术的创新使基因功能分析发生了革命性的变化。现在可以设计RNA干扰实验，针对基因组中的每一个基因并筛选特定的表型。拟议项目的最终目标是开发并在公共领域提供预测有效siRNAs的软件和一个数据库，其中包含一套经过功能验证的、目前已发现的所有人类、小鼠和大鼠基因的siRNAs。该计划的第一阶段将包括开发一种算法来预测最有效的siRNA，并开发一种高通量技术来分析几种模型mRNAs预测的siRNA的沉默效率。在第二阶段，该计划将扩展到开发一个数据库，其中包括一组经过功能验证的全基因组人类、小鼠和大鼠siRNA。第二阶段研究的另一个目标是将克隆在慢病毒载体中的经过功能验证的siRNA集合和全基因组siRNA文库作为商业产品发布。慢病毒载体中的siRNAs和siRNA文库的收集将允许在全球范围内搜索与各种疾病有关的功能基因，并通过在活细胞中任意选择灭活特定的mRNAs和相应的蛋白质来验证新的药物靶点。

DESCRIPTION (provided by applicant): Owing to the massive amount of data accumulated through various genome-wide sequencing and gene expression projects, there is an urgent need to develop novel bioinformatic tools and technologies to uncover the functions of each gene in the human genome. Recent innovations in gene knockdown technology, based on small interfering RNA (siRNA), have revolutionized gene functional analysis. It is now possible to design RNA interference experiments to target every gene in the genome and screen for specific phenotypes. The ultimate goal of the proposed project is to develop and make available, in the public domain, software for the prediction of effective siRNAs and a database with a functionally verified set of siRNAs for all currently discovered human, mouse and rat genes. Phase I of this program will cover the development of an algorithm for predicting the most efficient siRNAs and a high-throughput technology for the analysis of the silencing efficiency of the predicted siRNAs for several model mRNAs. At the Phase II, the program will be extended towards the development of a database with a genome-wide set of functionally verified human, mouse and rat siRNAs. Another goal of the Phase II studies is to release, as commercial products, a functionally verified collection of siRNAs and genome-wide siRNA libraries cloned in lentiviral vectors. The collection of siRNAs and siRNA libraries in lentiviral vectors will allow the performance of a global search for functional genes involved in a variety of diseases and to validate new drug targets by arbitrary selective inactivation of specific mRNAs and corresponding proteins in the context of the living cells.