Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
EMBO Mol Med. 2011 Apr;3(4):186-8. doi: 10.1002/emmm.201100132. Epub 2011 Mar 10.
Sequence-specific knockdown of gene expression is a goal that has been long sought by both basic and clinical investigators. In this regard, the discovery of RNA interference (RNAi) in was immediately recognized as a potential breakthrough for studying gene function (Fire et al, 1998). These findings demonstrated that double-stranded (ds)RNAs are triggers for sequence-specific, post-transcriptional gene silencing via targeted degradation of messenger RNAs harbouring a complementary sequence to one of the two strands. Initially, it was thought that such post-transcriptional regulation of gene expression could not be achieved in mammalian systems due to the strong induction of interferon by dsRNAs. This potential restriction was short lived with the demonstration that endonuclease processed dsRNAs of 21–25 nucleotides in length, designated small interfering RNAs (siRNAs), were able to elicit sequence-specific degradation of mRNAs in mammalian cells without triggering interferon responses (Elbashir et al, 2001). These findings provided a huge impetus to develop RNAi as a therapeutic modality. The dream to selectively block the expression of deleterious proteins and treat formerly non-drugable diseases led to the rapid establishment of new biotech companies and branches of major pharmaceutical companies devoted to RNAi therapeutics.
基因表达的序列特异性敲低是基础和临床研究人员长期追求的目标。在这方面，在 发现的 RNA 干扰 (RNAi) 立即被认为是研究基因功能的潜在突破（Fire 等人，1998 年）。这些发现表明，双链 (ds) RNA 是通过靶向降解含有与两条链之一互补序列的信使 RNA 来触发序列特异性转录后基因沉默的触发物。最初，由于 dsRNA 强烈诱导干扰素，人们认为这种对基因表达的转录后调控在哺乳动物系统中无法实现。这种潜在的限制是短暂的，因为证明了内切酶处理的 21-25 个核苷酸长的 dsRNA，称为小干扰 RNA (siRNA)，能够在不触发干扰素反应的情况下诱导哺乳动物细胞中 mRNA 的序列特异性降解（Elbashir 等人，2001 年）。这些发现为将 RNAi 开发为一种治疗方式提供了巨大的动力。选择性阻断有害蛋白表达和治疗以前不可用药的疾病的梦想，导致了新的生物技术公司和主要制药公司致力于 RNAi 治疗的分支机构的迅速建立。
