Issue 54, 2017, Issue in Progress
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RSC Advances

Antisense oligonucleotide modified with serinol nucleic acid (SNA) induces exon skipping in mdx myotubes†

Bao T. Le,ab   Keiji Murayama,c   Fazel Shabanpoor,d   Hiroyuki Asanumac  and  Rakesh N. Veedu ORCID logo *ab  

* Corresponding authors

a Centre for Comparative Genomics, Murdoch University, Perth, Australia-6150
E-mail: R.Veedu@murdoch.edu.au

b Perron Institute for Neurological and Translational Science, Perth, Australia-6009

c Department of Biomolecular Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan

d Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia

Abstract

Serinol nucleic acid (SNA) is a novel nucleic acid analogue that can form highly stable heteroduplexes with complementary DNA and RNA sequences. Structurally, SNA is a close mimic to peptide nucleic acid (PNA) which is widely used in diagnostic and therapeutic applications. SNA chemistry is relatively new, and so far the scope of SNA has only been explored in improving the efficacy of small interfering RNA and for developing a highly sensitive molecular beacon for diagnostic applications. In this study, we investigated the potential of SNA-modified antisense oligonucleotide (AO) in parallel to PNA-oligo for splice-modulation in an in vitro cellular model of Duchenne muscular dystrophy (DMD). We synthesized a 20-mer SNA and PNA antisense oligonucleotide (AO) designed to induce exon-23 skipping in the mouse dystrophin gene transcript. Our results demonstrated that the SNA AO induced exon-23 skipping at all tested concentrations, whereas the corresponding PNA AO failed to induce any exon-23 skipping upon 24 hours of transfection using Lipofectin transfection reagent. Our results further expands the potential of SNA oligonucleotides in therapeutic applications.

Graphical abstract: Antisense oligonucleotide modified with serinol nucleic acid (SNA) induces exon skipping in mdx myotubes

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Article information

DOI
https://doi.org/10.1039/C7RA06091B
Article type
Paper
Submitted
01 Jun 2017
Accepted
29 Jun 2017
First published
06 Jul 2017
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2017,7, 34049-34052

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Antisense oligonucleotide modified with serinol nucleic acid (SNA) induces exon skipping in mdx myotubes

B. T. Le, K. Murayama, F. Shabanpoor, H. Asanuma and R. N. Veedu, RSC Adv., 2017, 7, 34049 DOI: 10.1039/C7RA06091B

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