作者
Bao T Le, Suxiang Chen, Mikhail Abramov, Piet Herdewijn, Rakesh N Veedu
发表日期
2016
期刊
Chemical communications
卷号
52
期号
92
页码范围
13467-13470
出版商
Royal Society of Chemistry
简介
Antisense oligonucleotide (AO) mediated exon skipping has been widely explored as a therapeutic strategy for several diseases, in particular, for rare genetic disorders such as Duchenne muscular dystrophy (DMD). To date, the potential of anhydrohexitol nucleic acid (HNA), cyclohexenyl nucleic acid (CeNA) and altritol nucleic acid (ANA) has not been explored in exon skipping. For the first time, in this study we designed and synthesised HNA, CeNA and ANA-modified 2′-O-methyl (2′-OMe) mixmer AOs on a phosphorothioate (PS) backbone, and evaluated their potential to induce exon 23 skipping in mdx mouse myotubes, as a model system. Our results clearly showed that all three AO candidates modified with HNA, CeNA and ANA could efficiently induce Dmd exon 23 skipping in vitro in parallel to the fully modified 2′-OMePS AO with reduced dual exon 22/23 skipping. In addition, they showed high …
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