Algorithm and genome-wide database of functional siRNAs

描述（由申请人提供）：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）的基因敲低技术的创新，已经彻底改变了基因功能分析。现在有可能设计RNA干扰实验来针对基因组中的每个基因并筛选特定的表型。该项目的最终目标是在公共领域开发并提供有效sirna预测软件和一个包含所有目前发现的人类、小鼠和大鼠基因的功能验证sirna集的数据库。该项目的第一阶段将涵盖预测最有效sirna的算法的开发，以及用于分析几种模型mrna的预测sirna沉默效率的高通量技术。在第二阶段，该项目将扩展到开发一个包含全基因组功能验证的人类、小鼠和大鼠sirna的数据库。II期研究的另一个目标是作为商业产品发布在慢病毒载体上克隆的功能验证的siRNA集合和全基因组siRNA文库。慢病毒载体中siRNA和siRNA文库的收集将允许在全球范围内搜索涉及多种疾病的功能基因，并通过在活细胞背景下任意选择特定mrna和相应蛋白质的失活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.