Skipping Multiple Exons to Treat DMD—Promises and Challenges
Abstract
:1. Introduction
2. Advancements in Multi-Exon Skipping Therapy
2.1. Use of Antisense Oligonucleotides and Phosphorodiamidate Morpholino Oligomers for Single- and Multi-Exon Skipping
2.2. Exons 6–9 Multi-Exon Skipping Using PMOs in the Canine Model
2.3. Efficacy of Exons 6–9 Multi-Exon Skipping Using Peptide-Conjugated Morpholinos in the Heart of a Dog Model
2.4. Multi-Exon Skipping of Exons 3–9—A Potential Target for Therapy
2.5. Functional Correction of Dystrophin Actin-Binding Domain with DMD Exons 3–9 Deletion Using CRISPR/Cas9
- Generating del. Ex3–9 iPSCs by targeting introns 2 and 9 and the subsequent deletion of exons 3–7.
- Generating del. Ex6–9 iPSCs by targeting introns 5 and 7 and the subsequent deletion of exons 6–9.
- Generating del. Ex7–11 iPSCs by targeting introns 6 and 11 and the subsequent deletion of exons 7–11.
2.6. vPMO-Mediated Multi-Skipping of Exons 45–55 in Mdx52 Mice
2.7. CRISPR/Cas9 for Multi-Exon Skipping Targeting DMD Exons 52–53
3. Future Implications and Clinical Hurdles
Acknowledgments
Conflicts of Interest
References
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Aslesh, T.; Maruyama, R.; Yokota, T. Skipping Multiple Exons to Treat DMD—Promises and Challenges. Biomedicines 2018, 6, 1. https://doi.org/10.3390/biomedicines6010001
Aslesh T, Maruyama R, Yokota T. Skipping Multiple Exons to Treat DMD—Promises and Challenges. Biomedicines. 2018; 6(1):1. https://doi.org/10.3390/biomedicines6010001
Chicago/Turabian StyleAslesh, Tejal, Rika Maruyama, and Toshifumi Yokota. 2018. "Skipping Multiple Exons to Treat DMD—Promises and Challenges" Biomedicines 6, no. 1: 1. https://doi.org/10.3390/biomedicines6010001