Regulus Therapeutics, Inc., 1896 Rutherford Road, Carlsbad, CA 92008, USA.
Nat Rev Drug Discov. 2010 Jan;9(1):57-67. doi: 10.1038/nrd3010.
Small interfering RNAs (siRNAs) are widely used to study gene function owing to the ease with which they silence target genes, and there is considerable interest in their potential for therapeutic applications. In a remarkably short time since their discovery, siRNAs have entered human clinical trials in various disease areas. However, rapid acceptance of the use of siRNAs has been accompanied by recognition of several hurdles for the technology, including a lack of specificity. Off-target activity can complicate the interpretation of phenotypic effects in gene-silencing experiments and can potentially lead to unwanted toxicities. Here, we describe the types of off-target effects of siRNAs and methods to mitigate them, to help enable effective application of this exciting technology.
小干扰 RNA（siRNA）因其能够轻易沉默靶基因而被广泛用于研究基因功能，并且人们对其在治疗中的应用潜力也有着浓厚的兴趣。自发现以来，siRNA 在各种疾病领域的临床试验中进展迅速。然而，随着 siRNA 的广泛应用，人们也逐渐认识到该技术存在一些障碍，包括缺乏特异性。脱靶活性会使基因沉默实验中的表型效应的解释变得复杂，并且可能会导致不必要的毒性。在这里，我们描述了 siRNA 的脱靶效应类型以及减轻这些效应的方法，以帮助实现这项激动人心的技术的有效应用。
