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Synthesis of a morpholino nucleic acid (MNA)-Uridine phosphoramidite, and exon skipping using MNA/2′-O-Methyl mixmer antisense oligonucleotide

Chen, S., Le, B., Rahimizadeh, K., Shaikh, K., Mohal, N. and Veedu, R.N. (2016) Synthesis of a morpholino nucleic acid (MNA)-Uridine phosphoramidite, and exon skipping using MNA/2′-O-Methyl mixmer antisense oligonucleotide. Molecules, 21 (11). p. 1582.

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Abstract

In this study, we synthesised a morpholino nucleoside-uridine (MNA-U) phosphoramidite and evaluated the potential of a MNA-modified antisense oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes in vitro towards extending the applicability of morpholino chemistry with other nucleotide monomers. We designed, synthesised, and compared exon skipping efficiencies of 20 mer MNA-modified 2′-O-methyl RNA mixmer AO on a phosphorothioate backbone (MNA/2′-OMePS) to the corresponding fully modified 2′-O-methyl RNA AO (2′-OMePS) as a control. Our results showed that the MNA/2′-OMePS efficiently induced exon 23 skipping. As expected, the 2′-OMePS AO control yielded efficient exon 23 skipping. Under the applied conditions, both the AOs showed minor products corresponding to exon 22/23 dual exon skipping in low yield. As these are very preliminary data, more detailed studies are necessary; however, based on the preliminary results, MNA nucleotides might be useful in constructing antisense oligonucleotides.

Publication Type: Journal Article
Murdoch Affiliation: Centre for Comparative Genomics
Publisher: MDPI
Copyright: © 2016 MDPI AG
URI: http://researchrepository.murdoch.edu.au/id/eprint/34907
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