Open Access

Scientific Reports, volume 7, issue 1, publication number 3672

LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts

Touznik Aleksander ¹

Maruyama Rika ¹

Hosoki Kana ¹

Echigoya Yusuke ¹

Yokota Toshifumi ^{1, 2}

Hide authors affiliations Show authors affiliations: 2 affiliations

Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Canada |

The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Science Endowed Research Chair, Edmonton, Canada |

Publication type: Journal Article

Publication date: 2017-06-16

Springer Nature

Journal: Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor: 4.6

ISSN: 20452322

DOI: 10.1038/s41598-017-03850-2

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PubMed ID: 28623256

Multidisciplinary

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting motor neurons, and is currently the most frequent genetic cause of infant mortality. SMA is caused by a loss-of-function mutation in the survival motor neuron 1 (SMN1) gene. SMN2 is an SMN1 paralogue, but cannot compensate for the loss of SMN1 since exon 7 in SMN2 mRNA is excluded (spliced out) due to a single C-to-T nucleotide transition in the exon 7. One of the most promising strategies to treat SMA is antisense oligonucleotide (AON)-mediated therapy. AONs are utilized to block intronic splicing silencer number 1 (ISS-N1) on intron 7 of SMN2, which causes exon 7 inclusion of the mRNA and the recovery of the expression of functional SMN protein from the endogenous SMN2 gene. We developed novel locked nucleic acid (LNA)-based antisense oligonucleotides (LNA/DNA mixmers), which efficiently induce exon 7 inclusion in SMN2 and restore the SMN protein production in SMA patient fibroblasts. The mixmers are highly specific to the targeted sequence, and showed significantly higher efficacy than an all-LNA oligonucleotide with the equivalent sequence. These data suggest that use of LNA/DNA mixmer-based AONs may be an attractive therapeutic strategy to treat SMA.

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Citations by journals

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Citations by publishers

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Springer Nature	Springer Nature, 13, 31.71% Springer Nature 13 publications, 31.71%
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Elsevier	Elsevier, 3, 7.32% Elsevier 3 publications, 7.32%
Wiley	Wiley, 3, 7.32% Wiley 3 publications, 7.32%
Frontiers Media S.A.	Frontiers Media S.A., 1, 2.44% Frontiers Media S.A. 1 publication, 2.44%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 2.44% Public Library of Science (PLoS) 1 publication, 2.44%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 2.44% American Chemical Society (ACS) 1 publication, 2.44%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 1, 2.44% Royal Society of Chemistry (RSC) 1 publication, 2.44%
Taylor & Francis	Taylor & Francis, 1, 2.44% Taylor & Francis 1 publication, 2.44%
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Touznik A. et al. LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts // Scientific Reports. 2017. Vol. 7. No. 1. 3672

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Touznik A., Maruyama R., Hosoki K., Echigoya Y., Yokota T. LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts // Scientific Reports. 2017. Vol. 7. No. 1. 3672

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TY - JOUR

DO - 10.1038/s41598-017-03850-2

UR - https://doi.org/10.1038%2Fs41598-017-03850-2

TI - LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts

T2 - Scientific Reports

AU - Touznik, Aleksander

AU - Maruyama, Rika

AU - Hosoki, Kana

AU - Echigoya, Yusuke

AU - Yokota, Toshifumi

PY - 2017

DA - 2017/06/16 00:00:00

PB - Springer Nature

IS - 1

VL - 7

PMID - 28623256

SN - 2045-2322

ER -

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@article{2017_Touznik,

author = {Aleksander Touznik and Rika Maruyama and Kana Hosoki and Yusuke Echigoya and Toshifumi Yokota},

title = {LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts},

journal = {Scientific Reports},

year = {2017},

volume = {7},

publisher = {Springer Nature},

month = {jun},

url = {https://doi.org/10.1038%2Fs41598-017-03850-2},

number = {1},

doi = {10.1038/s41598-017-03850-2}

}

Found error?

Publisher

Springer Nature

Journal

Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor

4.6

ISSN

20452322 (Print)