Nature Communications (Jan 2019)
Next-generation muscle-directed gene therapy by in silico vector design
- S. Sarcar,
- W. Tulalamba,
- M. Y. Rincon,
- J. Tipanee,
- H. Q. Pham,
- H. Evens,
- D. Boon,
- E. Samara-Kuko,
- M. Keyaerts,
- M. Loperfido,
- E. Berardi,
- S. Jarmin,
- P. In’t Veld,
- G. Dickson,
- T. Lahoutte,
- M. Sampaolesi,
- P. De Bleser,
- T. VandenDriessche,
- M. K. Chuah
Affiliations
- S. Sarcar
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- W. Tulalamba
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- M. Y. Rincon
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- J. Tipanee
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- H. Q. Pham
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- H. Evens
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- D. Boon
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- E. Samara-Kuko
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- M. Keyaerts
- Nuclear Medicine Department, UZ Brussel & In vivo Cellular and Molecular Imaging Lab, Vrije Universiteit Brussel (VUB)
- M. Loperfido
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- E. Berardi
- Translational Cardiomyology Laboratory, Embryo and Stem Cell Biology Unit, Department of Development and Regeneration, University of Leuven
- S. Jarmin
- School of Biological Sciences, Royal Holloway, University of London, Egham
- P. In’t Veld
- Department of Pathology, Diabetes Research Center, Vrije Universiteit Brussel (VUB)
- G. Dickson
- School of Biological Sciences, Royal Holloway, University of London, Egham
- T. Lahoutte
- Nuclear Medicine Department, UZ Brussel & In vivo Cellular and Molecular Imaging Lab, Vrije Universiteit Brussel (VUB)
- M. Sampaolesi
- Translational Cardiomyology Laboratory, Embryo and Stem Cell Biology Unit, Department of Development and Regeneration, University of Leuven
- P. De Bleser
- VIB Center for Inflammation Research and Department of Biomedical Molecular Biology, Ghent University
- T. VandenDriessche
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- M. K. Chuah
- Department of Gene Therapy & Regenerative Medicine, Vrije Universiteit Brussel (VUB)
- DOI
- https://doi.org/10.1038/s41467-018-08283-7
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 16
Abstract
Adeno-associated viral vectors (AAV) are being developed for gene therapy of skeletal muscle, but it is a challenge to achieve robust gene expression. Here, the authors identify muscle-specific cisregulatory elements that lead to a substantial increase in micro-dystrophin and follistatin expression, resulting in a safe and sustainable rescue of the dystrophic phenotype in mouse models.
