Issue 86, 2017

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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
05 Oct 2017
Accepted
21 Nov 2017
First published
28 Nov 2017
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2017,7, 54542-54545

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

B. T. Le, M. Hornum, P. K. Sharma, P. Nielsen and R. N. Veedu, RSC Adv., 2017, 7, 54542 DOI: 10.1039/C7RA10964D

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