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Specificity of short interfering RNA determined through gene expression signatures

机译：通过基因表达特征确定短干扰RNA的特异性

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摘要

Short interfering RNA (siRNA) is widely used for studying gene function and holds great promise as a tool for validating drug targets and treating disease. A critical assumption in these applications is that the effect of siRNA on cells is specific, i.e., limited to the specific knockdown of the target gene. In this article, we characterize the specificity of siRNA by applying gene expression profiling. Several siRNAs were designed against different regions of the same target gene for three different targets. Their effects on cells were compared by using DNA microarrays to generate gene expression signatures. When the siRNA design and transfection conditions were optimized, the signatures for different siRNAs against the same target were shown to correlate very closely, whereas the signatures for different genes revealed no correlation. These results indicate that siRNA is a highly specific tool for targeted gene knockdown, establishing siRNA-mediated gene silencing as a reliable approach for large-scale screening of gene function and drug target validation. [References: 35]
机译：短干扰RNA（siRNA）被广泛用于研究基因功能，并有望作为验证药物靶点和治疗疾病的工具。在这些应用中的关键假设是siRNA对细胞的作用是特异性的，即限于靶基因的特异性敲低。在本文中，我们通过应用基因表达谱来表征siRNA的特异性。针对三个不同的靶标，针对同一靶标基因的不同区域设计了几种siRNA。通过使用DNA微阵列产生基因表达特征，比较了它们对细胞的作用。当优化siRNA设计和转染条件时，针对同一靶标的不同siRNA的签名显示出非常紧密的相关性，而不同基因的签名则没有相关性。这些结果表明，siRNA是用于靶向基因敲低的高度特异性工具，将siRNA介导的基因沉默确立为大规模筛选基因功能和药物靶标验证的可靠方法。 [参考：35]

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