Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides

被引：11

作者：

Masaki, Yoshiaki ^{[1
]}

Iriyama, Yusuke ^{[2
]}

Nakajima, Hiroyuki ^{[3
]}

Kuroda, Yusuke ^{[3
]}

Kanaki, Tatsuro ^{[3
]}

Furukawa, Satoshi ^{[3
]}

Sekine, Mitsuo ^{[1
]}

Seio, Kohji ^{[1
]}

机构：

[1] Tokyo Inst Technol, Dept Life Sci & Technol, 4259 Nagatsuta Midoriku, Yokohama, Kanagawa 2268501, Japan

[2] Nissan Chem Corp, Chem Res Labs, Funabashi, Chiba, Japan

[3] Nissan Chem Corp, Biol Res Labs, Shiraoka, Japan

来源：

NUCLEIC ACID THERAPEUTICS | 2018年 / 28卷 / 05期

关键词：

RNase-H-dependent antisense; N-Methylcarbamoylethyl (MCE) modification; hepatotoxicity; SHOW IMPROVED POTENCY; MESSENGER-RNA; HEPATOTOXICITY;

D O I：

10.1089/nat.2018.0738

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An RNase H-dependent antisense oligonucleotide (ASO), having the 2-O-(2-N-methylcarbamoylethyl) (MCE) modification, was evaluated in vitro and in vivo. The antisense activities of an ASO having the MCE modification were comparable with those of an ASO having the 2-O-methoxyethyl (MOE) modification in both in vitro and in vivo experiments. In contrast, the hepatotoxic potential of the ASO having the MCE modification was lower than that of the ASO having the MOE modification. Thus, these findings suggested that the MCE modification could be used as an alternative to the MOE modification.

引用

页码：307 / 311

页数：5

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