Chemistry, Properties, and in Vitro and in Vivo Applications of 2'-O-Methoxyethyl-4'-thioRNA, a Novel Hybrid Type of Chemically Modified RNA
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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2-O-甲氧基乙基-4-thioRNA（一种新型混合型化学修饰 RNA）的化学、性质以及体外和体内应用
作者：
Saito;Y.; Hashimoto;Y.; Arai;M.; Tarashima;N.; Miyazawa;T.; Miki;K.; Takahashi;M.; Furukawa;K.; Yamazaki;N.; Matsuda;A.; Ishida,T.; Minakawa;N.
我们报道了2′-O-甲氧基乙基-4 ′-硫代RNA（莫伊-SRNA）的合成、性质以及在体外和体内的应用。在与互补RNA的杂交中，莫伊-SRNA显示Tm值适度改善（相对于RNA：RNA双链体+3.4 °C）。然而，莫伊-SRNA相对于2′-O-甲氧基乙基RNA（MOERNA）、2′-O-甲基-4 ′-硫代RNA（Me-SRNA）、2 ′-O-甲基RNA（MeRNA）、4′-硫代RNA（SRNA）和天然RNA的核酸酶稳定性的综合比较结果显示，莫伊-SRNA具有最高的稳定性（人血浆中t1/2>48 h）。由于莫伊-SRNA的有利性质，我们评估了其作为针对miR-21的抗microRNA寡核苷酸的体外和体内效力。尽管莫伊-SRNA的体外效力中等，但其体内效力对抑制肿瘤生长具有显著意义（与MOERNA相似）。
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 ofTmvalue (+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).