Next Article in Journal
Clinical-Grade Human Pluripotent Stem Cells for Cell Therapy: Characterization Strategy
Previous Article in Journal
Molecular Characterization of Tc964, A Novel Antigenic Protein from Trypanosoma cruzi
Open AccessArticle

Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro

1
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150 Australia
2
Perron Institute for Neurological and translational Science, Perth 6005, Australia
3
School of Statistics, Henan University of Economics and Law, Zhengzhou 450001, China
4
Nucleic Acid Center, Department of Physics and Chemistry and Pharmacy, University of Southern Denmark, M 5230 Odense, Denmark
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2434; https://doi.org/10.3390/ijms21072434
Received: 19 February 2020 / Revised: 27 March 2020 / Accepted: 29 March 2020 / Published: 31 March 2020
(This article belongs to the Section Molecular Biology)
Alpha-l-Locked nucleic acid (α-l-LNA) is a stereoisomeric analogue of locked nucleic acid (LNA), which possesses excellent biophysical properties and also exhibits high target binding affinity to complementary oligonucleotide sequences and resistance to nuclease degradations. Therefore, α-l-LNA nucleotides could be utilised to develop stable antisense oligonucleotides (AO), which can be truncated without compromising the integrity and efficacy of the AO. In this study, we explored the potential of α-l-LNA nucleotides-modified antisense oligonucleotides to modulate splicing by inducing Dmd exon-23 skipping in mdx mouse myoblasts in vitro. For this purpose, we have synthesised and systematically evaluated the efficacy of α-l-LNA-modified 2′-O-methyl phosphorothioate (2′-OMePS) AOs of three different sizes including 20mer, 18mer and 16mer AOs in parallel to fully-modified 2′-OMePS control AOs. Our results demonstrated that the 18mer and 16mer truncated AO variants showed slightly better exon-skipping efficacy when compared with the fully-23 modified 2′-OMePS control AOs, in addition to showing low cytotoxicity. As there was no previous report on using α-l-LNA-modified AOs in splice modulation, we firmly believe that this initial study could be beneficial to further explore and expand the scope of α-l-LNA-modified AO therapeutic molecules. View Full-Text
Keywords: α-l-LNA; locked nucleic acids; antisense oligonucleotides; DMD α-l-LNA; locked nucleic acids; antisense oligonucleotides; DMD
Show Figures

Figure 1

MDPI and ACS Style

Raguraman, P.; Wang, T.; Ma, L.; Jørgensen, P.T.; Wengel, J.; Veedu, R.N. Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro. Int. J. Mol. Sci. 2020, 21, 2434. https://doi.org/10.3390/ijms21072434

AMA Style

Raguraman P, Wang T, Ma L, Jørgensen PT, Wengel J, Veedu RN. Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro. International Journal of Molecular Sciences. 2020; 21(7):2434. https://doi.org/10.3390/ijms21072434

Chicago/Turabian Style

Raguraman, Prithi; Wang, Tao; Ma, Lixia; Jørgensen, Per T.; Wengel, Jesper; Veedu, Rakesh N. 2020. "Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro" Int. J. Mol. Sci. 21, no. 7: 2434. https://doi.org/10.3390/ijms21072434

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop