Therapeutic Potential of Tricyclo-DNA Antisense Oligonucleotides

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2016 Nov 18

PMID 27854216

Citations 19

Authors

Aurelie Goyenvalle

Christian Leumann

Luis Garcia

Affiliations

Soon will be listed here.

Abstract

Oligonucleotide therapeutics hold great promise for the treatment of various diseases and the antisense field is constantly gaining interest due to the development of more potent and nuclease resistant chemistries. Despite a rather low success rate with only three antisense drugs being clinically approved, the frontiers of AON therapeutic applications have increased over the past three decades and continue to expand thanks to a steady increase in understanding the mechanisms of action of these molecules, progress in chemical modification and delivery.In this review, we will examine the recent advances obtained with the tricyclo-DNA chemistry which displays unique pharmacological properties and unprecedented uptake in many tissues after systemic administration. We will review their specific properties and their therapeutic applications mainly for neuromuscular disorders, including exon-skipping for Duchenne muscular dystrophy and exon-inclusion for spinal muscular atrophy, but also aberrant splicing correction for Pompe disease. Finally, we will discuss their advantages and potential limitations, with a focus on the need for careful toxicological screen early in the process of AON drug development.

Citing Articles

Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.

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

Blitek M, Phongsavanh X, Goyenvalle A RSC Med Chem. 2024; 15(9):3017-3025.

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Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.

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Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy.

Marchesi E, Cortesi R, Preti L, Rimessi P, Sguizzato M, Bovolenta M Int J Mol Sci. 2022; 23(8).

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Common and Rare 5'UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics.

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