title: Chemistry, properties, and in vitro and in vivo applications of 2'-O-methoxyethyl-4'-thioRNA, a novel hybrid type of chemically modified RNA.
abstract: We report the synthesis, properties, and in vitro and in vivo applications of 2'-O-methoxyethyl-4'-thioRNA (MOE-SRNA), a novel type of hybrid chemically modified RNA. In its hybridization with complementary RNA, MOE-SRNA showed a moderate improvement of Tm value (+3.4 °C relative to an RNA:RNA duplex). However, the results of a comprehensive comparison of the nuclease stability of MOE-SRNA relative to 2'-O-methoxyethylRNA (MOERNA), 2'-O-methyl-4'-thioRNA (Me-SRNA), 2'-O-methylRNA (MeRNA), 4'-thioRNA (SRNA), and natural RNA revealed that MOE-SRNA had the highest stability (t1/2 >48 h in human plasma). Because of the favorable properties of MOE-SRNA, we evaluated its in vitro and in vivo potencies as an anti-microRNA oligonucleotide against miR-21. Although the in vitro potency of MOE-SRNA was moderate, its in vivo potency was significant for the suppression of tumor growth (similar to that of MOERNA).
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505 (Japan).
authors.forename: Yota
authors.initials: Y
authors.lastname: Saito
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Mai
authors.initials: M
authors.lastname: Arai
authors.forename: Noriko
authors.initials: N
authors.lastname: Tarashima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furukawa
authors.forename: Naoshi
authors.initials: N
authors.lastname: Yamazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Noriaki
authors.initials: N
authors.lastname: Minakawa
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000473:pathology; D009690:Nucleic Acid Conformation; D012313:RNA / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020871:RNA Stability; D014407:Tumor Cells, Cultured
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012313:RNA
keywords: RNA; anti-microRNA; chemically modified oligonucleotide; in vivo activity; inhibitors