Morris K V, Rossi J J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 91010, USA.
Gene Ther. 2006 Mar;13(6):553-8. doi: 10.1038/sj.gt.3302688.
Lentiviral vectors portend a promising system to deliver antiviral genes for treating viral infections such as HIV-1 as they are capable of stably transducing both dividing and nondividing cells. Recently, small interfering RNAs (siRNAs) have been shown to be quite efficacious in silencing target genes. RNA interference is a natural mechanism, conserved in nature from Yeast to Humans, by which siRNAs operate to specifically and potently down regulate the expression of a target gene either transcriptionally (targeted to DNA) or post-transcriptionally (targeted to mRNA). The specificity and relative simplicity of siRNA design insinuate that siRNAs will prove to be favorable therapeutic agents. Since siRNAs are a small nucleic acid reagents, they are unlikely to elicit an immune response and genes encoding these siRNAs can be easily manipulated and delivered by lentiviral vectors to target cells. As such, lentiviral vectors expressing siRNAs represent a potential therapeutic approach for the treatment of viral infections such as HIV-1. This review will focus on the development, lentiviral based delivery, and the potential therapeutic use of siRNAs in treating viral infections.
慢病毒载体预示着一种很有前景的系统,可用于递送抗病毒基因来治疗诸如HIV-1等病毒感染,因为它们能够稳定转导分裂细胞和非分裂细胞。最近,小干扰RNA(siRNA)已被证明在沉默靶基因方面非常有效。RNA干扰是一种自然机制,从酵母到人类在自然界中保守,通过该机制siRNA可转录(靶向DNA)或转录后(靶向mRNA)特异性且有效地下调靶基因的表达。siRNA设计的特异性和相对简单性表明siRNA将被证明是有利的治疗剂。由于siRNA是小核酸试剂,它们不太可能引发免疫反应,并且编码这些siRNA的基因可以很容易地通过慢病毒载体操纵并递送至靶细胞。因此,表达siRNA的慢病毒载体代表了治疗诸如HIV-1等病毒感染的潜在治疗方法。本综述将重点关注siRNA在治疗病毒感染方面的发展、基于慢病毒的递送以及潜在的治疗用途。