Synthesis of 2'-O-(N-methylcarbamoylethyl) 5-methyl-2-thiouridine and its application to splice-switching oligonucleotides.


Department of Life Science and Technology, Tokyo Institute of Technology, 4259 J2-16, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan. Electronic address: [Email]


The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5-methyl-2-thiouridine (s2TMCE), a duplex-stabilizing nucleotide with an MCE modification, into SSOs further improved splice switching. These SSOs may be useful for the treatment of genetic diseases associated with splicing errors.


2′-O-modification,Chemically modified RNA,Exon skipping,Nucleic acid therapeutics,Splice-switching oligonucleotide,