[RNA interference and its application in inhibiting HIV-1 infection]

Abstract

RNA interfering (RNAi)--one of the most exciting discoveries in biology in the last couple decades has quickly become one of the most powerful and indispensable tools in the molecular biologist's toolkit. It is an important protection mechanism in cells, by which animals and plants defend viral infection and inhibit viral replication. RNAi is the process of sequence-specific, posttranscriptional gene silencing in animals and plants initiated by dsRNA that is homologous to the silenced gene and has emerged as a powerful tool to silence gene expression in multiple organisms. It has recently been shown that double-stranded, small interfering RNAs (siRNAs) of 21-25 nucleotides can be transfected into relevant cells to target specific RNAs. In mammalian cells it is known that dsRNA 30 base pairs or longer can trigger interferon responses that are intrinsically sequence-nonspecific, thus limiting the application of RNAi as an experimental and therapeutic agent. Duplexes of 19-25 nts (nucleotides) siRNA with short 3' overhangs, however, can efficiently inhibit gene expression in a sequence-specific manner in cultured mammalian cells. This approach was utilized to inhibit human immunodeficiency virus type I (HIV-1) infection in human cells. The in vitro experiments indicate that RNAi as a powerful antiviral tool will bring a promising future to gene therapy for virus disease.