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Chemistry, Properties, and in Vitro and in Vivo Applications of 2′‐ O ‐Methoxyethyl‐4′‐thioRNA, a Novel Hybrid Type of Chemically Modified RNA
Author(s) -
Saito Yota,
Hashimoto Yosuke,
Arai Mai,
Tarashima Noriko,
Miyazawa Tadashi,
Miki Kazuya,
Takahashi Mayumi,
Furukawa Kazuhiro,
Yamazaki Naoshi,
Matsuda Akira,
Ishida Tatsuhiro,
Minakawa Noriaki
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402398
Subject(s) - transfer rna , rna , in vivo , in vitro , chemistry , oligonucleotide , nuclease , biochemistry , microbiology and biotechnology , dna , biology , gene , genetics
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 T m 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 ( t 1/2 >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).