RNA干扰技术

RNA Interference Technology

RNA干扰首次发现于美丽线虫,siRNAs(小干扰RNA)的产生可诱导特异内源性mRNA的降解,现在被认为是真核细胞在翻译后水平抑制蛋白产生的主要途径。典型的内源性siRNA是由19-23个碱基构成的双链寡核苷酸RNA,由RNase蛋白复合物聚集降解靶mRNA所产生。RNA干扰最近常被用作逆转录基因工具来沉默多倍体有机体中的基因表达。表达siRNAs的方法日新月异,已经由最初的在体内或者体外利用病毒载体转染合成的siRNA至细胞,发展为在不同型细胞和有机体中建立不同功能的特异蛋白。RNA干扰的方法较之前的方法(反义DNA或抗体封闭技术)在抑制基因表达方面有着明显的优点。RNAi序列特异性的抑制效应是有选择性的、长期的,系统地调节靶向基因。不论是直接转染siRNA或者由RNA载体表达产生,RNAi都可抑制哺乳动物中的特异基因,这无疑加速了基因功能的研究速度,而且极有潜力成为高效的基因特异性治疗方法。药理学家一直梦寐以求可有方法能够选择性的拮抗或剔除个体特异蛋白的功能,RNAi十分有望使其梦想成真。

The technology is first discovered in plant the nematode Caenorhabditis elegans. The production of small interfering RNAs （siRNAs） that bind to and induce the degradation of specific endogenous mRNAs is now recognized as a mechanism widely employed by eukaryotic cells to inhibit protein production at a posttranscriptional level. The endogenous siRNAs that upon 23-base double -stranded RNA oligonucleotides, produced from much larger RNAs that upon binding to target mRNAs recruit RNases to a protein complex that degrades the targeted mRNA. RNAi（RNA interference） has recently emerged as a powerful reverse genetic tool to silence gene expression in multiple organisms. Methods for expressing siRNAs in cells in culture and in vivo using viral vectors, and for transfecting cells with synthetic siRNAs, have been developed and are being used to establish the functions of specific proteins in various cell types and organisms. RNA interference methods provide several major advantages over prior methods （antisenseDNA or antibody-based technipues） for suppressing gene expression. The general and sepuence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality. It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. Pharmacologists have long dreamed of the ability to selectively antagonize or to eliminate the function of individual proteins--RNAi technology may eventrally make that dream a reality.