Chemistry,Properties, and in Vitro and in Vivo Applications of 2′‐O‐Methoxyethyl‐4′‐thioRNA,a Novel Hybrid Type of Chemically Modified RNA |
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| Authors: | Yota Saito Yosuke Hashimoto Mai Arai Noriko Tarashima Tadashi Miyazawa Kazuya Miki Dr Mayumi Takahashi Prof Dr Kazuhiro Furukawa Prof Dr Naoshi Yamazaki Prof Dr Akira Matsuda Prof Dr Tatsuhiro Ishida Prof Dr Noriaki Minakawa |
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| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1‐78‐1 Shomachi, Tokushima 770‐8505 (Japan);2. Faculty of Pharmaceutical Sciences, Hokkaido University, Kita‐12, Nishi‐6, Kita‐ku, Sapporo 060‐0812 (Japan) |
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| 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). |
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| Keywords: | anti‐microRNA chemically modified oligonucleotide in vivo activity inhibitors RNA |
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