UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.

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. Green open access

[img]
Preview
Text
Muntoni_molecules-22-00563.pdf - ["content_typename_Published version" not defined]

Download (1MB) | Preview

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 > Provost and Vice Provost Offices
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 Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Genetics and Genomic Medicine Prog
URI: http://discovery.ucl.ac.uk/id/eprint/1549495
Downloads since deposit
60Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item