Page 10 - Read Online

Scherman. Rare Dis Orphan Drugs J 2023;2:12 Rare Disease and
DOI: 10.20517/rdodj.2023.01
Orphan Drugs Journal

Review Open Access

RNA antisense and silencing strategies using
synthetic drugs for rare muscular and

neuromuscular diseases

Daniel Scherman 1,2
1
Foundation for Rare Diseases, 96 rue Didot, Paris 75014, France.
2
Université Paris Cité, Faculté de sciences pharmaceutiques et biologiques, Unité de Technologies Chimiques et Biologiques pour
la Santé (UTCBS), CNRS UMR8258, Paris 75014, France.
Correspondence to: Prof. Daniel Scherman, Faculté de sciences pharmaceutiques et biologiques, Unité de Technologies
Chimiques et Biologiques pour la Santé (UTCBS), CNRS UMR8258, Inserm U1267, 4, avenue de l'observatoire, Paris 75014,
France. E-mail: daniel.scherman@parisdescartes.fr

How to cite this article: Scherman D. RNA antisense and silencing strategies using synthetic drugs for rare muscular and
neuromuscular diseases. Rare Dis Orphan Drugs J 2023;2:12. https://dx.doi.org/10.20517/rdodj.2023.01

Received: 12 Jan 2023 Revised: 16 May 2023 Accepted: 25 May 2023 Published: 5 Jun 2023
Academic Editor: Gillian Butler-Browne Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
Rare diseases occur in their large majority from a genetic cause, which makes them good candidates for genetic
RNA drugs. The basic concepts, principles, mechanisms of action and chemical optimizations of synthetic
antisense oligonucleotides (ASO) and small interfering RNA (siRNA) are illustrated. These drugs act either by
leading to RNA degradation, or as steric blockers of RNA translation, microRNA antagonists, splicing modulators or
inducers of exon skipping. Chemical modifications and delivery techniques differ and are adapted to their distinct
functions. The successes, potential, and challenges of synthetic RNA drugs are illustrated for several muscular and
neuromuscular diseases: Duchenne muscular dystrophy, spinal muscular atrophy, transthyretin amyloidosis, Type 1
myotonic dystrophy, centronuclear myopathy, oculopharyngeal muscular dystrophy.

Keywords: Antisense oligonucleotide, neuromuscular disorders, rare disease, RNA drug, RNA interference, small
interfering siRNA

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

www.rdodjournal.com