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

ABSTRACT: 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.

SUBMITTER: Masaki Y

PROVIDER: S-EPMC6157346 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Masaki Yoshiaki Y Iriyama Yusuke Y Nakajima Hiroyuki H Kuroda Yusuke Y Kanaki Tatsuro T Furukawa Satoshi S Sekine Mitsuo M Seio Kohji K

Nucleic acid therapeutics 20180718 5

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 finding ...[more]

PMID: 30020852

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