title: Therapeutic Potential of Tricyclo-DNA antisense oligonucleotides.
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.
authors.affiliation: Université de Versailles St- Quentin, U1179 INSERM, UFR des Sciences de la Santé - LIA BAHN CSM, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Goyenvalle
authors.affiliation: Department of Chemistry & Biochemistry, University of Bern, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Leumann
authors.affiliation: Université de Versailles St- Quentin, U1179 INSERM, UFR des Sciences de la Santé - LIA BAHN CSM, France.
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
mesh_terms: D016373:DNA, Antisense / Q000627:therapeutic use*; D005091:Exons; D015316:Genetic Therapy; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy* / Q000235:genetics; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics; D009468:Neuromuscular Diseases / Q000188:drug therapy / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012326:RNA Splicing
chemical_list: D016373:DNA, Antisense; D016376:Oligonucleotides, Antisense
keywords: Antisense oligonucleotides; delivery; exon-reinclusion; exon-skipping; nanoparticles; splicing correction