4.3 Article

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

Journal

NUCLEIC ACID THERAPEUTICS
Volume 28, Issue 5, Pages 307-311

Publisher

MARY ANN LIEBERT, INC
DOI: 10.1089/nat.2018.0738

Keywords

RNase-H-dependent antisense; N-Methylcarbamoylethyl (MCE) modification; hepatotoxicity

Funding

  1. JSPS KAKENHI [17H04886, 26810086]
  2. Grants-in-Aid for Scientific Research [17H04886, 26810086] Funding Source: KAKEN

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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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