title: Lentivirus-mediated RNA interference therapy for human immunodeficiency virus type 1 infection.
abstract: RNA interference (RNAi) is a natural mechanism by which small interfering RNAs (siRNAs) operate to specifically and potently downregulate the expression of a target gene. This downregulation has been demonstrated by targeting siRNAs to the mRNA (posttranscriptional gene silencing) as well as to the gene promoter, regulating gene expression epigenetically by transcriptional gene silencing. These observations significantly broaden the role RNA plays in the cell and suggest that siRNAs could prove to be a potent future therapeutic for the treatment of diseases such as human immunodeficiency virus type 1 (HIV-1) infection. The specificity and simplicity of design and the ability to express siRNAs from mammalian promoters make the use of siRNAs to target and suppress virtually any gene or gene promoter of interest a soon-to-be-realized technology. However, the delivery and stable expression of siRNAs to target cells remain an enigma that could be surmounted, at least regarding the treatment of HIV-1 infection, by the application of lentiviral vectors to deliver and express anti-HIV-1 siRNAs in target cells. This review focuses on the development, delivery, and potential therapeutic use of antiviral siRNAs in treating HIV-1.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Morris
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
mesh_terms: D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008954:Models, Biological; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D034741:RNA, Small Interfering