title: Optimizing siRNA delivery to the genital mucosa.
abstract: RNA interference (RNAi) describes a highly conserved pathway, present in eukaryotic cells, for regulating gene expression. Small stretches of double-stranded RNA, termed small interfering RNAs (siRNAs), utilize this pathway to bind homologous mRNA, resulting in site-specific mRNA cleavage and subsequent protein degradation. The ubiquitous presence of the RNAi machinery, combined with its specificity and efficacy, makes it an attractive mechanism for reducing aberrant gene expression in therapeutic settings. However, a major obstacle to utilizing RNAi in the clinic is siRNA delivery. Administered siRNAs must make contact with the appropriate cell types and, following internalization, gain access to the cytosol where the RNAi machinery resides. This must be achieved so that silencing is maximized, whilst minimizing any undesirable off-target effects. Recently, the utility of siRNAs as a microbicide, usually applied to the genital mucosa for preventing transmission of sexually transmitted diseases including HIV-1 and HSV-2, has been investigated. In this review we will describe these studies and discuss potential strategies for improving gene silencing.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Katakowski
authors.forename: Deborah
authors.initials: D
authors.lastname: Palliser
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005835:Genitalia / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D034741:RNA, Small Interfering