Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy
Abstract
:1. Introduction
2. Gene-Replacement Strategies Using Virus Vectors
2.1. Choice of Vector
Tissue type | Effective serotype | Reference |
---|---|---|
Neurons and glial cells | AAV9, AAV7 > AAV8 > AAV5 > AAV2, AAV1 | [26,27,28] |
Glioblastoma | AAV8, AAV7 > AAV6 > AAV2 > AAV5 | [28] |
Cardiac tissue | AAV9 > AAV8 > AAV1, AAV6 > AAV2 | [29,30,31,32] |
Muscle (systemic) | AAV8 | [33,34] |
Muscle (local) | AAV1, AAV6 | [33,35,36,37] |
Liver (hepatocytes) | AAV9, AAV8 | [38] |
Pancreas | AAV8, AAV1 | [39,40] |
Retina | AAV8, AAV5 > AAV4 > AAV1, AAV2 | [41,42,43] |
Dendritic cells | AAV6 | [44] |
Hematopoietic stem cells | AAV1 | [45] |
Fibroblasts | AAV1, AAV6 > AAV2 | [46] |
2.2. Modification of the Dystrophin GENE
2.3. Use of Surrogate Genes
3. AAV-Mediated Transduction of Large Animal Models
3.1. Vector Production
3.2. Canine Models for the Gene Transduction Study
3.3. Immunological Issues of rAAV
3.4. Intravascular Vector Administration by Limb Perfusion
3.5. Global Muscle Therapies
4. Safety and Potential Impact of Clinical Trials
4.1. Clinical Trials for Muscle Transduction
4.2. Gene Therapy Medicine
5. Future Perspectives
5.1. Modification of mRNA Splicing with rAAV-mediated Exon-Skipping
5.2. Pharmacological Intervention
5.3. Capsid Modification
5.4. AAV-Mediated Gene and Cell Therapy
5.5. Targeted Vector Integration
6. Conclusions
Acknowledgments
Conflict of Interest
References
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Okada, T.; Takeda, S. Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy. Pharmaceuticals 2013, 6, 813-836. https://doi.org/10.3390/ph6070813
Okada T, Takeda S. Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy. Pharmaceuticals. 2013; 6(7):813-836. https://doi.org/10.3390/ph6070813
Chicago/Turabian StyleOkada, Takashi, and Shin'ichi Takeda. 2013. "Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy" Pharmaceuticals 6, no. 7: 813-836. https://doi.org/10.3390/ph6070813
APA StyleOkada, T., & Takeda, S. (2013). Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy. Pharmaceuticals, 6(7), 813-836. https://doi.org/10.3390/ph6070813