Rational design of small interfering RNA for genome-wide target knockdown

 描述（由申请人提供）：RNA干扰（RNAi）是活细胞内小RNA引导的基因沉默过程。RNAi技术被广泛用于生物学研究和临床应用，因为它具有基本上敲除任何感兴趣基因的能力。然而，RNAi研究中一个尚未解决的主要问题是非特异性基因沉默。众所周知，除了单个预期的基因靶标之外，许多非预期的靶标也同时沉默。因此，迫切需要开发用于改善RNAi特异性的新方法。RNAi的特异性和效力由沉默复合物中的小干扰RNA（siRNA）决定。我们提出的假设，基因沉默的特异性可以显着提高与合理的siRNA设计。我们之前已经开发了一种用于设计广泛分布的商业siRNA的机器学习算法。基于这一商业上的成功，我们建议进一步开发一种新的方法，用于下一代siRNA的全基因组设计，并显着降低脱靶效应。新的设计方法将为进一步商业化开发可用于各种基于RNAi的应用的siRNA产品奠定坚实的基础。

 DESCRIPTION (provided by applicant): RNA interference (RNAi) is a small RNA-guided gene silencing process within living cells. The RNAi technique is widely used in both biological research and clinical applications because it has the ability to knockdown essentially any gene of interest. However, one major unresolved issue in RNAi studies is non-specific gene silencing. It is well known that, in addition to the single intended gene target, many unintended targets are also simultaneously silenced. Thus, there is an urgent need to develop new methods for improving RNAi specificity. RNAi specificity and potency are determined by the small interfering RNA (siRNA) in the silencing complex. We propose the hypothesis that gene silencing specificity can be significantly improved with rational siRNA design. We have previously developed a machine learning algorithm for the design of widely-distributed commercial siRNAs. Based on this commercial success, we propose to further develop a new method for genome-wide design of next-generation siRNAs with significantly reduced off-target effects. The new design method will lay a solid foundation for further commercial development of siRNA products that can be used in a variety of RNAi-based applications.