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

 描述(申请人提供)：RNA干扰(RNAi)是活细胞内一种由RNA引导的小基因沉默过程。RNAi技术被广泛应用于生物学研究和临床应用，因为它基本上能够敲除任何感兴趣的基因。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外，许多非预期的靶标也同时被沉默。因此，迫切需要开发新的方法来提高RNAi的特异性。RNAi的特异性和效力由沉默复合体中的小干扰RNA(SiRNA)决定。我们提出的假设是，通过合理的siRNA设计可以显著提高基因沉默的特异性。我们之前已经开发了一种机器学习算法，用于设计广泛分布的商业siRNA。在这一商业成功的基础上，我们建议进一步开发一种新的方法来设计下一代siRNA的全基因组，并显著减少脱靶效应。新的设计方法将为siRNA产品的进一步商业化开发奠定坚实的基础，这些产品可以用于各种基于RNAi的应用。

 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.