Morris Kevin V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Biotechniques. 2006 Apr;Suppl:7-13. doi: 10.2144/000112166.
RNA interference (RNAi) and specifically the use of small interfering RNAs (siRNAs) represents a potentially new paradigm in gene knockout technology. Clearly siRNAs can be used to knockdown the expression of a targeted transcript in what has been termed posttranscriptional gene silencing (PTGS). While there are a plethora of reports applying siRNA-mediated PTGS the limitation of the duration of the effect remains. Recently, in human cells, siRNAs have been shown, similar to plants and Schizosaccharomyces pombe, to mediate transcriptional gene silencing (TGS). The observation that siRNAs can function in a TGS manner in human cells suggests that, similar to plants, human genes may also be able to be silenced more permanently via epigenetic modifications. The ramifications of siRNA-mediated TGS in humans suggest that longer term suppression of gene function can be obtained via siRNA-directed chromatin modifications. Undoubtedly the potential to employ siRNA technology is broader than once envisioned in human cells and suggests that siRNA-mediated TGS is not simply limited to PTGS. The potential to utilize siRNAs to direct epigenetic changes in local chromatin structure offers a new therapeutic avenue that could prove remarkably robust and of immeasurable therapeutic value in the directed control of target gene expression.
RNA干扰（RNAi），特别是小干扰RNA（siRNA）的应用，代表了基因敲除技术中一种潜在的新范例。显然，siRNA可用于在所谓的转录后基因沉默（PTGS）中降低靶向转录本的表达。虽然有大量关于应用siRNA介导的PTGS的报道，但这种效应的持续时间有限。最近，在人类细胞中，siRNA已被证明与植物和粟酒裂殖酵母类似，能够介导转录基因沉默（TGS）。siRNA在人类细胞中以TGS方式发挥作用这一观察结果表明，与植物类似，人类基因或许也能够通过表观遗传修饰被更持久地沉默。siRNA介导的TGS在人类中的影响表明，通过siRNA指导的染色质修饰可以实现基因功能的长期抑制。毫无疑问，在人类细胞中应用siRNA技术的潜力比以往设想的更为广泛，这表明siRNA介导的TGS并不局限于PTGS。利用siRNA指导局部染色质结构的表观遗传变化的潜力提供了一条新的治疗途径，这在定向控制靶基因表达方面可能被证明非常强大且具有不可估量的治疗价值。
