Issue 9, 2024

The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy

Abstract

The development of antisense oligonucleotide (ASO)-based therapeutics has made tremendous progress over the past few years, in particular for the treatment of neuromuscular disorders such as Duchenne muscular dystrophy and spinal muscular atrophy. Several ASO drugs have now reached market approval for these diseases and many more are currently under clinical evaluation. Among them, ASOs made of the tricyclo-DNA originally developed by Christian Leumann have shown particularly interesting properties and demonstrated promise for the treatment of Duchenne muscular dystrophy. In this review, we examine the bench to bedside journey of tricyclo-DNA-ASOs from their early preclinical evaluation as fully phosphorotiated-ASOs to the latest generation of lipid-conjugated-ASOs. Finally we discuss the remaining challenges of ASO-mediated exon-skipping therapy for DMD and future perspectives for this promising chemistry of ASOs.

Graphical abstract: The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy

Article information

Article type
Review Article
Submitted
29 May 2024
Accepted
18 Jul 2024
First published
19 Jul 2024

RSC Med. Chem., 2024,15, 3017-3025

The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy

M. Blitek, X. Phongsavanh and A. Goyenvalle, RSC Med. Chem., 2024, 15, 3017 DOI: 10.1039/D4MD00394B

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