Journal article
Rational design of short locked Nucleic Acid-Modified 2′- O -Methyl antisense oligonucleotides for efficient exon-skipping in vitro
Molecular Therapy - Nucleic Acids, Vol.9, pp.155-161
2017
Abstract
Locked nucleic acid is a prominent nucleic acid analog with unprecedented target binding affinity to cDNA and RNA oligonucleotides and shows remarkable stability against nuclease degradation. Incorporation of locked nucleic acid nucleotides into an antisense oligonucleotide (AO) sequence can reduce the length required without compromising the efficacy. In this study, we synthesized a series of systematically truncated locked nucleic acid-modified 2′-O-methyl AOs on a phosphorothioate (PS) backbone that were designed to induce skipping exon 23 from the dystrophin transcript in H-2Kb-tsA58 mdx mouse myotubes in vitro. The results clearly demonstrated that shorter AOs (16- to 14-mer) containing locked nucleic acid nucleotides efficiently induced dystrophin exon 23 skipping compared with the corresponding 2′-O-methyl AOs. Our remarkable findings contribute significantly to the existing knowledge about the designing of short LNA-modified oligonucleotides for exon-skipping applications, which will help reduce the cost of exon-skipping AOs and potential toxicities, particularly the 2′-OMe-based oligos, by further reducing the length of AOs.
Details
- Title
- Rational design of short locked Nucleic Acid-Modified 2′- O -Methyl antisense oligonucleotides for efficient exon-skipping in vitro
- Authors/Creators
- B.T. Le (Author/Creator) - Perron Institute for Neurological and Translational ScienceA.M. Adams (Author/Creator) - Murdoch UniversityS. Fletcher (Author/Creator) - Murdoch UniversityS.D. Wilton (Author/Creator) - Murdoch UniversityR.N. Veedu (Author/Creator) - Murdoch University
- Publication Details
- Molecular Therapy - Nucleic Acids, Vol.9, pp.155-161
- Publisher
- Elsevier
- Identifiers
- 991005540021507891
- Copyright
- © 2017 The Author(s).
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 2 Chemistry
- 2.170 Nucleic Acids Chemistry
- 2.170.988 Oligonucleotide Modifications
- Web Of Science research areas
- Medicine, Research & Experimental
- ESI research areas
- Biology & Biochemistry