1. ¹Department of Molecular and Experimental Medicine, Division of Rheumatology, The Scripps Research Institute, La Jolla, CA, USA
2. ²Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA

Correspondence: Dr JJ Rossi, Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Rd, Duarte, CA 91010, USA. E-mail: JRossi@coh.org

Received 28 July 2005; Revised 7 September 2005; Accepted 21 October 2005; Published online 5 January 2006.

Abstract

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 downregulate 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.