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

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...

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Autores principales: Masaki, Yoshiaki, Iriyama, Yusuke, Nakajima, Hiroyuki, Kuroda, Yusuke, Kanaki, Tatsuro, Furukawa, Satoshi, Sekine, Mitsuo, Seio, Kohji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2018
Materias:
Original Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157346/
https://www.ncbi.nlm.nih.gov/pubmed/30020852
http://dx.doi.org/10.1089/nat.2018.0738
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author Masaki, Yoshiaki
Iriyama, Yusuke
Nakajima, Hiroyuki
Kuroda, Yusuke
Kanaki, Tatsuro
Furukawa, Satoshi
Sekine, Mitsuo
Seio, Kohji
author_facet Masaki, Yoshiaki
Iriyama, Yusuke
Nakajima, Hiroyuki
Kuroda, Yusuke
Kanaki, Tatsuro
Furukawa, Satoshi
Sekine, Mitsuo
Seio, Kohji
author_sort Masaki, Yoshiaki
collection PubMed
description 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.
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spelling pubmed-61573462018-09-27 Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides Masaki, Yoshiaki Iriyama, Yusuke Nakajima, Hiroyuki Kuroda, Yusuke Kanaki, Tatsuro Furukawa, Satoshi Sekine, Mitsuo Seio, Kohji Nucleic Acid Ther Original Articles 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. Mary Ann Liebert, Inc., publishers 2018-10-01 2018-09-24 /pmc/articles/PMC6157346/ /pubmed/30020852 http://dx.doi.org/10.1089/nat.2018.0738 Text en © Yoshiaki Masaki et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited.
spellingShingle Original Articles
Masaki, Yoshiaki
Iriyama, Yusuke
Nakajima, Hiroyuki
Kuroda, Yusuke
Kanaki, Tatsuro
Furukawa, Satoshi
Sekine, Mitsuo
Seio, Kohji
Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title_full Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title_fullStr Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title_full_unstemmed Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title_short Application of 2′-O-(2-N-Methylcarbamoylethyl) Nucleotides in RNase H-Dependent Antisense Oligonucleotides
title_sort application of 2′-o-(2-n-methylcarbamoylethyl) nucleotides in rnase h-dependent antisense oligonucleotides
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157346/
https://www.ncbi.nlm.nih.gov/pubmed/30020852
http://dx.doi.org/10.1089/nat.2018.0738
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