title: Gene silencing by 2'-O-methyldithiomethyl-modified siRNA, a prodrug-type siRNA responsive to reducing environment.
abstract: RNAs bearing various 2'-modifications have been synthesized in an effort to improve nuclease resistance. However, the gene silencing activity of small interfering RNAs (siRNAs) has been decreased or sometimes completely suppressed by the chemical modifications. We previously developed a post-synthetic approach for the synthesis of 2'-O-methyldithiomethyl-modified RNA, which can be converted into unmodified RNA under reducing conditions, and named it Reducing-Environment-Dependent Uncatalyzed Chemical Transforming RNA (REDUCT RNA). Here, the gene silencing activity of REDUCT siRNA bearing 2'-O-methyldithiomethyl groups was evaluated. REDUCT siRNA showed more effective gene silencing than unmodified siRNA regardless of the modification site. This result suggests that REDUCT siRNA is converted into unmodified siRNA inside cells as a prodrug-type siRNA.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ochi
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Imai
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Junsuke
authors.initials: J
authors.lastname: Hayashi
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Shun-Ichi
authors.initials: SI
authors.lastname: Wada
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: urata@gly.oups.ac.jp.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Urata
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D011355:Prodrugs; D034741:RNA, Small Interfering
keywords: 2′-O-Methyldithiomethyl modification; Prodrug-type RNA; Reducing environment; siRNA