Algorithm for selection of functional siRNA sequences
Algorithm for selection of functional siRNA sequences
复制标题
DOI：
10.1016/j.bbrc.2004.02.157
复制
发表时间：
2004-04-16
影响因子：
3.1
通讯作者：
Prydz, H
中科院分区：
文献类型：
--
作者：
Amarzguioui, M;Prydz, H
随机设计的siRNA靶向同一mRNA中的不同位置，显示出广泛不同的活性。我们对46种siRNA进行了统计分析，确定了19bp双工的各种特征，这些特征与70%敲低水平的功能显著相关，并通过最近由其他人报道的34种siRNA的独立数据集验证了这些结果。在两个数据集中，与功能始终呈正相关的特征包括双工端稳定性的不对称性（通过双工两端三个末端碱基对的A/U差来测量）和基序S1、A6和W19。motif U1或G19的存在与功能缺失有关。基于这些发现的一种选择算法在两个数据集中强烈区分了siRNA的两个功能群，并且在用于设计针对新的内源性人类基因的siRNA时被证明是非常有效的。(C) 2004爱思唯尔公司版权所有。
Randomly designed siRNA targeting different positions within the same mRNA display widely differing activities. We have performed a statistical analysis of 46 siRNA, identifying various features of the 19bp duplex that correlate significantly with functionality at the 70% knockdown level and verified these results against an independent data set of 34 siRNA recently reported by others. Features that consistently correlated positively with functionality across the two data sets included an asymmetry in the stability of the duplex ends (measured as the A/U differential of the three terminal basepairs at either end of the duplex) and the motifs S1, A6, and W19. The presence of the motifs U1 or G19 was associated with lack of functionality. A selection algorithm based on these findings strongly differentiated between the two functional groups of siRNA in both data sets and proved highly effective when used to design siRNA targeting new endogenous human genes. (C) 2004 Elsevier Inc. All rights reserved.