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Recent Advances in AON-Mediated Exon-Skipping Therapy for Duchenne Muscular Dystrophy

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Abstract

The accelerated approval of eteplirsen (renamed Exondys51™) by US Food and Drug Administration (FDA) garnered renewed enthusiasm for antisense oligonucleotide (AON)-mediated exon-skipping therapies within the Duchenne muscular dystrophy (DMD) community. However, this approval is not without dissent, particularly from within the FDA committee, originating from the discordance between functional improvements seen in patients and lack of efficacy at the cellular level. Undoubtedly, improvements in exon-skipping efficiency and delivery of AONs would go a long way to quell doubts on the applicability of this approach in DMD. Several novel strategies have been developed to enhance exon-skipping efficiency. These include modification of the backbone chemistry of AONs (e.g. tricyclo-DNA and peptide nucleic acid) or conjugation of a peptide (e.g. cell-penetrating peptide or muscle-targeting peptide) with AON and the use of adjuvants including hexose and dantrolene. Here, we examine recent developments in these areas and discuss the likelihood of future clinical application and limitations of these approaches.

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  1. Department of Cell Biology, Tianjin Medical University, Tianjin, China

    Xianjun Gao, Gang Han & HaiFang Yin

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  1. Xianjun Gao
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  2. Gang Han
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  3. HaiFang Yin
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Correspondence to HaiFang Yin .

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Editors and Affiliations

  1. Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA, Department of Biomedical Sciences College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Department of Bioengineering, University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  2. Department of Pediatrics Nationwide Children’s Hospital and Research Institute, Department of Neurology Nationwide Children’s Hospital and Research Institute, The Ohio State University, Columbus, OH, USA

    Jerry R. Mendell

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Gao, X., Han, G., Yin, H. (2019). Recent Advances in AON-Mediated Exon-Skipping Therapy for Duchenne Muscular Dystrophy. In: Duan, D., Mendell, J. (eds) Muscle Gene Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-03095-7_19

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