RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing

Neuromuscular disorders represent multifaceted abnormal conditions, with little or no cure, leading to patient deaths from complete muscle wasting and atrophy. Despite strong efforts in the past decades, development of effective treatments is still urgently needed. Advent of next-generation sequenci...

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Autores principales:	Veronica Verdile, Gloria Guizzo, Gabriele Ferrante, Maria Paola Paronetto
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	alternative splicing neuromuscular disease RNA-based therapies Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bfdf39e3e7f3450d90d8cdf0f18f3cf7
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spelling	oai:doaj.org-article:bfdf39e3e7f3450d90d8cdf0f18f3cf72021-11-25T17:07:58ZRNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing10.3390/cells101128502073-4409https://doaj.org/article/bfdf39e3e7f3450d90d8cdf0f18f3cf72021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2850https://doaj.org/toc/2073-4409Neuromuscular disorders represent multifaceted abnormal conditions, with little or no cure, leading to patient deaths from complete muscle wasting and atrophy. Despite strong efforts in the past decades, development of effective treatments is still urgently needed. Advent of next-generation sequencing technologies has allowed identification of novel genes and mutations associated with neuromuscular pathologies, highlighting splicing defects as essential players. Deciphering the significance and relative contributions of defective RNA metabolism will be instrumental to address and counteract these malignancies. We review here recent progress on the role played by alternative splicing in ensuring functional neuromuscular junctions (NMJs), and its involvement in the pathogenesis of NMJ-related neuromuscular disorders, with particular emphasis on congenital myasthenic syndromes and muscular dystrophies. We will also discuss novel strategies based on oligonucleotides designed to bind their cognate sequences in the RNA or targeting intermediary of mRNA metabolism. These efforts resulted in several chemical classes of RNA molecules that have recently proven to be clinically effective, more potent and better tolerated than previous strategies.Veronica VerdileGloria GuizzoGabriele FerranteMaria Paola ParonettoMDPI AGarticlealternative splicingneuromuscular diseaseRNA-based therapiesBiology (General)QH301-705.5ENCells, Vol 10, Iss 2850, p 2850 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alternative splicing neuromuscular disease RNA-based therapies Biology (General) QH301-705.5
spellingShingle	alternative splicing neuromuscular disease RNA-based therapies Biology (General) QH301-705.5 Veronica Verdile Gloria Guizzo Gabriele Ferrante Maria Paola Paronetto RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
description	Neuromuscular disorders represent multifaceted abnormal conditions, with little or no cure, leading to patient deaths from complete muscle wasting and atrophy. Despite strong efforts in the past decades, development of effective treatments is still urgently needed. Advent of next-generation sequencing technologies has allowed identification of novel genes and mutations associated with neuromuscular pathologies, highlighting splicing defects as essential players. Deciphering the significance and relative contributions of defective RNA metabolism will be instrumental to address and counteract these malignancies. We review here recent progress on the role played by alternative splicing in ensuring functional neuromuscular junctions (NMJs), and its involvement in the pathogenesis of NMJ-related neuromuscular disorders, with particular emphasis on congenital myasthenic syndromes and muscular dystrophies. We will also discuss novel strategies based on oligonucleotides designed to bind their cognate sequences in the RNA or targeting intermediary of mRNA metabolism. These efforts resulted in several chemical classes of RNA molecules that have recently proven to be clinically effective, more potent and better tolerated than previous strategies.
format	article
author	Veronica Verdile Gloria Guizzo Gabriele Ferrante Maria Paola Paronetto
author_facet	Veronica Verdile Gloria Guizzo Gabriele Ferrante Maria Paola Paronetto
author_sort	Veronica Verdile
title	RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
title_short	RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
title_full	RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
title_fullStr	RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
title_full_unstemmed	RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing
title_sort	rna targeting in inherited neuromuscular disorders: novel therapeutic strategies to counteract mis-splicing
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bfdf39e3e7f3450d90d8cdf0f18f3cf7
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RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing

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