Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy

  title={Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy},
  author={Kasia Dzierlega and Toshifumi Yokota},
  journal={Gene Therapy},
Duchenne muscular dystrophy (DMD) is one of the most common lethal muscle-wasting disorders affecting young boys caused by mutations in the DMD gene. Exon skipping has emerged as a promising therapy for DMD. Antisense oligonucleotides (AONs) are designed to induce the skipping of exon(s), in order to restore the reading frame, and therefore, allow for dystrophin expression. Eteplirsen and golodirsen, AONs for DMD exons 51 and 53 skipping, have been recently approved by the FDA. Viltolarsen, an… 

Pharmacology and toxicology of eteplirsen and SRP-5051 for DMD exon 51 skipping: an update

This paper reviews and discusses the available information on the efficacy, safety, and tolerability data of eteplirsen and SRP-5051 from preclinical and clinical trials.

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A review of recent scientific and clinical progress of ASO and other novel RNA manipulations, including RNA-based editing using MS2 coat protein-conjugated adenosine deaminase acting on the RNA (MCP-ADAR) system illustrating the efficacy and limitations of therapies to restore dystrophin.

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A comprehensive compilation on gene-based therapeutic strategies and critically evaluate the approaches relative to its efficacy and feasibility while addressing their current limitations is provided.

Targeted exon skipping of NF1 exon 17 as a therapeutic for neurofibromatosis type I

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Additional therapies have the potential to help patients with DMD, although most are several years away from approval for patient use.

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Development of Antisense‐Mediated Exon Skipping as a Treatment for Duchenne Muscular Dystrophy

An overview of the available mouse models and it is proposed that different chemistries should be further developed in parallel in order to hasten the transfer of the exon skipping therapy to the clinic.

Optimizing exon skipping therapies for DMD.

  • T. YokotaW. DuddyT. Partridge
  • Biology
    Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
  • 2007
A review of recent progress in exon skipping therapy for Duchenne Muscular Dystrophy summarizes recent progress and discusses future strategies.

Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy

The challenges associated with primary muscle cell lines are illustrated and a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies is described.

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy

A cocktail of antisense morpholinos targeting exon 6 and exon 8 was designed and it restored dystrophin expression in body-wide skeletal muscles and evaluation of the efficacy and safety of multi-exon skipping in the CXMD dog model are presented.

Exon‐skipping therapy for Duchenne muscular dystrophy

  • A. NakamuraS. Takeda
  • Biology, Medicine
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2009
The genetic basis of DMD is summarized, and the potential and perspectives of exon skipping as a promising therapy for this disease are summarized.

Therapeutic exon skipping for dysferlinopathies?

The dysferlin protein domains and DYSF mutations are analyzed and what exons are promising targets with regard to applicability and feasibility are described and it is shown that DysF exon skipping seems to be as straightforward as DMD exon skipped, as AONs to induce efficient skipping of four DYSf exons were readily identified.

Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients.

The broad therapeutic applicability of the antisense-induced skipping of targeted exons from the pre-mRNA is demonstrated in cultured muscle cells from six DMD patients carrying different deletions and a nonsense mutation, restoring dystrophin synthesis in over 75% of cells.

Bodywide skipping of exons 45–55 in dystrophic mdx52 mice by systemic antisense delivery

A unique successful demonstration of effective rescue by exon 45–55 skipping in a dystrophin-deficient animal model is demonstrated.

Exons 45-55 Skipping Using Mutation-Tailored Cocktails of Antisense Morpholinos in the DMD Gene.

  • Y. EchigoyaK. Lim T. Yokota
  • Biology, Medicine
    Molecular therapy : the journal of the American Society of Gene Therapy
  • 2019