Nucleobase-modified antisense oligonucleotides containing 5-(phenyltriazol)-2′-deoxyuridine nucleotides induce exon-skipping: In vitro

Bao T. Le, Mick Hornum, Pawan K. Sharma, Poul Nielsen, Rakesh N. Veedu*

*Corresponding author for this work

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Chemically-modified antisense oligonucleotide-mediated exon-skipping has been validated as a therapeutic strategy for tackling several disease pathologies, particularly duchenne muscular dystrophy. To date, only sugar-modified and internucleotide linkage-modified oligonucleotide chemistries have been explored for exon-skipping applications. Herein, for the first time, we have investigated the potential of nucleobase-modified antisense oligonucleotides to induce exon-skipping. For this purpose, we have synthesised 5-(phenyltriazol)-2′-deoxyuridine-modified 2′-O-methyl mixmer antisense oligonucleotides, and evaluated their efficacy to induce exon-23 skipping in H-2Kb-tsA58 (H2K) mdx mouse myotubes as a model system. Our results showed that the phenyltriazol base-modified AOs successfully induced efficient exon-skipping in a DMD transcript. Our findings open up the exploration of novel base-modified antisense oligonucleotides for exon-skipping applications.

Original languageEnglish
JournalRSC Advances
Issue number86
Pages (from-to)54542-54545
Publication statusPublished - 2017


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