Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messengerRNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation.Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.
Hutch inson-G ilford早老症(HGPS)为一种极为罕见的遗传性疾病,发生率1/8000000,特征性表现为患儿以极快速度衰老,多数死于冠脉病变引起的心肌梗死或广泛动脉粥样硬化导致的卒中,平均寿命13岁。绝大多数HGPS病例病因为LMNA基因第11个外显子发生点突变(G608G),生成的突变lam in A由显性负效应造成细胞核结构和功能受损。目前该病已有几种动物模型,实验性治疗可以在体外将出泡的细胞核恢复正常。HGPS是研究衰老和心血管疾病机制的一个极好的模型。
