Induction of the interferon response by siRNA is cell type- and duplex length-dependent
Induction of the interferon response by siRNA is cell type- and duplex length-dependent
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DOI：
10.1261/rna.2340906
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发表时间：
2006-06-01
期刊：
影响因子：
4.5
通讯作者：
Khvorova, Anastasia
中科院分区：
文献类型：
--
作者：
Reynolds, Angela;Anderson, Emily M.;Khvorova, Anastasia
长链（27-29-bp双链RNA）Dicer依赖性底物已被鉴定为HEK 293和HeLa细胞中RNA干扰诱导基因敲除的有效介质。由于这些分子的长度据报道低于通常被认为是诱导哺乳动物干扰素（IFN）应答所必需的阈值，因此这些长siRNA被认为是研究和治疗环境中的RNAi底物。在这份报告中，我们证明了> 23-bp的dsRNA可以影响细胞活力，并以细胞类型特异性的方式诱导有效的IFN应答（通过dsRNA受体Toll样受体3的强烈上调而突出显示）。这一发现表明，siRNA诱导IFN应答的长度阈值不是固定的，而是在不同细胞类型之间显著变化。考虑到组成整个生物体的细胞类型的多样性，这些发现表明，在考虑RNAi实验中dsRNA分子的长度变化时，特别是在治疗应用中，应非常小心。
Long (27-29-bp dsRNA) Dicer-dependent substrates have been identified as potent mediators of RNAi-induced gene knockdown in HEK293 and HeLa cells. As the lengths of these molecules are reported to be below the threshold generally regarded as necessary for induction of the mammalian interferon (IFN) response, these long siRNA are being considered as RNAi substrates in both research and therapeutic settings. In this report, we demonstrate that > 23-bp dsRNA can influence cell viability and induce a potent IFN response (highlighted by a strong up-regulation of the dsRNA receptor, Toll-like receptor 3) in a cell type-specific manner. This finding suggests that the length threshold for siRNA induction of the IFN response is not fixed but instead varies significantly among different cell types. Given the diversity of cell types that comprise whole organisms, these findings suggest great care should be taken when considering length variations of dsRNA molecules for RNAi experimentation, especially in therapeutic applications.