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Molecules 2016, 21(11), 1582;

Synthesis of a Morpholino Nucleic Acid (MNA)-Uridine Phosphoramidite, and Exon Skipping Using MNA/2′-O-Methyl Mixmer Antisense Oligonucleotide

Centre for Comparative Genomics, Murdoch University, Perth 6150, Australia
Western Australian Neuroscience Research Institute, Perth 6150, Australia
GMK Research Laboratories Pvt. Ltd., Mallapur, Hyderabad 500 076, India
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 21 September 2016 / Revised: 11 November 2016 / Accepted: 16 November 2016 / Published: 22 November 2016
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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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. View Full-Text
Keywords: morpholino nucleotide; PMO; exon skipping; antisense oligonucleotide morpholino nucleotide; PMO; exon skipping; antisense oligonucleotide

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Chen, S.; Le, B.T.; Rahimizadeh, K.; Shaikh, K.; Mohal, N.; Veedu, R.N. Synthesis of a Morpholino Nucleic Acid (MNA)-Uridine Phosphoramidite, and Exon Skipping Using MNA/2′-O-Methyl Mixmer Antisense Oligonucleotide. Molecules 2016, 21, 1582.

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