Reduced base-base interactions between the DNA seed and RNA target are the major determinants of a significant reduction in the off-target effect due to DNA-seed-containing siRNA

K. Ui-Tei, K. Nishi, Y. Naito, S. Zenno, Aya Juni, K. Saigo
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引用次数: 2

Abstract

Previously, we showed that DNA replacement of the seed-containing region of class I siRNAs significantly reduced the off-target effect without substantial loss of target gene silencing activity (Ui-Tei et al, Nucleic Acids Res., 36, 2136–2151, 2008). Separately, we also showed that the level of the off-target effect due to non-modified class I siRNA is determined primarily by the calculated melting temperature (Tm) of the seed-target duplex, indicating that, at least in class I-siRNA-mediated gene silencing, Tm or thermodynamic stability of the complex between the siRNA seed and target mRNA is the most important factor determining the degree of off-target effects (Ui-Tei et al., Nucleic Acids Res., 36, 7100–7109, 2008). Here, using non-modified siRNAs other than class I siRNAs and DNA-seed-containing siRNAs, we examined the relationship between the thermodynamic stability of the seed-target duplex and the degree of the off-target effect. We found that the degree of the off-target effects is generally determined primarily by the Tm of the corresponding seed-target duplex, indicating that its thermodynamic stability is the most important general determinant of the degree of the off-target effect in gene silencing.
DNA种子和RNA靶标之间碱基相互作用的减少是由于含有DNA种子的siRNA而导致脱靶效应显著减少的主要决定因素
在此之前,我们发现,替换I类sirna含种子区域的DNA可显著降低脱靶效应,而不会显著降低靶基因沉默活性(Ui-Tei等人,核酸研究,36,2136-2151,2008)。另外,我们还发现,由未修饰的I类siRNA引起的脱靶效应水平主要由种子-靶双链的计算熔融温度(Tm)决定,这表明,至少在I类siRNA介导的基因沉默中,Tm或siRNA种子和靶mRNA之间复合物的热力学稳定性是决定脱靶效应程度的最重要因素(Ui-Tei等人,核酸研究,36,7100-7109,2008)。在这里,我们使用非I类sirna和含有dna种子的sirna之外的未修饰sirna,研究了种子-靶标双工的热力学稳定性与脱靶效应程度之间的关系。我们发现脱靶效应的程度通常主要由相应的种子-目标双链的Tm决定,这表明它的热力学稳定性是基因沉默中脱靶效应程度的最重要的一般决定因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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