title: Platination of the siRNA sense-strand modulates both efficacy and selectivity in vitro.
abstract: The use of short interfering RNAs (siRNA) for selective suppression of protein production has rapidly become a commonly used technique for transient modulation of protein levels. In the present paper, we investigate whether introduction of platinated bases in the sense strand can be used to modulate the efficacy of siRNAs. Four different siRNAs were studied, all targeting the initial AU-rich 3' UTR of Wnt-5a mRNA. The siRNAs were characterized with respect to melting properties and translational inhibitory effect in vitro using luciferase as a reporter gene. The translation inhibition studies reveal that all platinated siRNA remain efficient. For an siRNA with partial complementarity to the luciferase gene, platination was shown to reduce the off-target effects. All siRNAs were found to be active in cellular in vitro translation systems, reaching suppression levels well above 80% for the majority of siRNAs investigated.
authors.affiliation: Biokemi, Kemicentrum, Lunds Universitet, Box 124, SE-221 00 Lund, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Hägerlöf
authors.forename: Hanna
authors.initials: H
authors.lastname: Hedman
authors.forename: Sofi K C
authors.initials: SK
authors.lastname: Elmroth
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry; D002460:Cell Line; D002945:Cisplatin / Q000737:chemistry; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000494:pharmacology; D013696:Temperature; D051153:Wnt Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D002945:Cisplatin