Sardone, V;
Zhou, H;
Muntoni, F;
Ferlini, A;
Falzarano, MS;
(2017)
Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.
Molecules
, 22
(4)
, Article 563. 10.3390/molecules22040563.
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Abstract
Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules.
| Type: | Article |
|---|---|
| Title: | Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease. |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/molecules22040563 |
| Publisher version: | http://dx.doi.org/10.3390/molecules22040563 |
| Language: | English |
| Additional information: | © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Duchenne Muscular Dystrophy, Spinal Muscular Atrophy, antisense oligonucleotides, clinical trials, oligonucleotides delivery, Animals, Biological Transport, Cell-Penetrating Peptides, Clinical Trials as Topic, Drug Evaluation, Preclinical, Gene Transfer Techniques, Genetic Therapy, Humans, Muscular Atrophy, Spinal, Muscular Dystrophy, Duchenne, Neuromuscular Diseases, Oligonucleotides, Antisense, RNA Splicing, RNA, Messenger |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1549495 |
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