Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 4 November 2004
Science 3 December 2004:
Vol. 306. no. 5702, pp. 1796 - 1799
DOI: 10.1126/science.1104297
Prev | Table of Contents | Next

Reports

Rescue of Dystrophic Muscle Through U7 snRNA-Mediated Exon Skipping

Aurélie Goyenvalle,1 Adeline Vulin,1 Françoise Fougerousse,1 France Leturcq,2 Jean-Claude Kaplan,2 Luis Garcia,1 Olivier Danos1*

Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mouse, by a single administration of an AAV vector expressing antisense sequences linked to a modified U7 small nuclear RNA. We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy.

1 Généthon & CNRS UMR 8115, 1, rue de l'Internationale, Evry, France.
2 Laboratoire de Biochimie et de Génétique Moléculaire, Hôpital et Institut Cochin, 123 boulevard de Port-Royal, Paris, France.

* To whom correspondence should be addressed. E-mail: danos{at}genethon.fr

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Rescue of coagulation factor VII function by the U1+5A snRNA.
M. Pinotti, D. Balestra, L. Rizzotto, I. Maestri, F. Pagani, and F. Bernardi (2009)
Blood 113, 6461-6464
   Abstract »    Full Text »    PDF »
Delivery of bifunctional RNAs that target an intronic repressor and increase SMN levels in an animal model of spinal muscular atrophy.
T. D. Baughan, A. Dickson, E. Y. Osman, and C. L. Lorson (2009)
Hum. Mol. Genet. 18, 1600-1611
   Abstract »    Full Text »    PDF »
Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function.
H. Yin, H. M. Moulton, Y. Seow, C. Boyd, J. Boutilier, P. Iverson, and M. J.A. Wood (2008)
Hum. Mol. Genet. 17, 3909-3918
   Abstract »    Full Text »    PDF »
Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer.
B. Wu, H. M. Moulton, P. L. Iversen, J. Jiang, J. Li, J. Li, C. F. Spurney, A. Sali, A. D. Guerron, K. Nagaraju, et al. (2008)
PNAS 105, 14814-14819
   Abstract »    Full Text »    PDF »
AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis.
A. Buj-Bello, F. Fougerousse, Y. Schwab, N. Messaddeq, D. Spehner, C. R. Pierson, M. Durand, C. Kretz, O. Danos, A.-M. Douar, et al. (2008)
Hum. Mol. Genet. 17, 2132-2143
   Abstract »    Full Text »    PDF »
Gene Therapy in Heart Failure.
L. E. Vinge, P. W. Raake, and W. J. Koch (2008)
Circ. Res. 102, 1458-1470
   Abstract »    Full Text »    PDF »
U1-snRNA-mediated rescue of mRNA processing in severe factor VII deficiency.
M. Pinotti, L. Rizzotto, D. Balestra, M. A. Lewandowska, N. Cavallari, G. Marchetti, F. Bernardi, and F. Pagani (2008)
Blood 111, 2681-2684
   Abstract »    Full Text »    PDF »
Generation and Characterization of Transgenic Mice with the Full-length Human DMD Gene.
P. A. C. 't Hoen, E. J. de Meijer, J. M. Boer, R. H. A. M. Vossen, R. Turk, R. G. H. J. Maatman, K. E. Davies, G.-J. B. van Ommen, J. C. T. van Deutekom, and J. T. den Dunnen (2008)
J. Biol. Chem. 283, 5899-5907
   Abstract »    Full Text »    PDF »
Dentofacial characteristics of growing patients with Duchenne muscular dystrophy: a morphological study.
C. Morel-Verdebout, S. Botteron, and S. Kiliaridis (2007)
Eur J Orthod 29, 500-507
   Abstract »    Full Text »    PDF »
Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications.
A. Aartsma-Rus and G.-J. B. van Ommen (2007)
RNA 13, 1609-1624
   Abstract »    Full Text »    PDF »
uPA deficiency exacerbates muscular dystrophy in MDX mice.
M. Suelves, B. Vidal, A. L. Serrano, M. Tjwa, J. Roma, R. Lopez-Alemany, A. Luttun, M. M. de Lagran, M. A. Diaz, M. Jardi, et al. (2007)
J. Cell Biol. 178, 1039-1051
   Abstract »    Full Text »    PDF »
Zebrafish relatively relaxed mutants have a ryanodine receptor defect, show slow swimming and provide a model of multi-minicore disease.
H. Hirata, T. Watanabe, J. Hatakeyama, S. M. Sprague, L. Saint-Amant, A. Nagashima, W. W. Cui, W. Zhou, and J. Y. Kuwada (2007)
Development 134, 2771-2781
   Abstract »    Full Text »    PDF »
Consensus document on European brain research.
J. Olesen, M. G Baker, T. Freund, M. di Luca, J. Mendlewicz, I. Ragan, and M. Westphal (2006)
J. Neurol. Neurosurg. Psychiatry 77, i1-i49
   Abstract »    Full Text »    PDF »
Defective splicing, disease and therapy: searching for master checkpoints in exon definition.
E. Buratti, M. Baralle, and F. E. Baralle (2006)
Nucleic Acids Res. 34, 3494-3510
   Abstract »    Full Text »    PDF »
Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model.
M. A. Denti, A. Rosa, G. D'Antona, O. Sthandier, F. G. De Angelis, C. Nicoletti, M. Allocca, O. Pansarasa, V. Parente, A. Musaro, et al. (2006)
PNAS 103, 3758-3763
   Abstract »    Full Text »    PDF »
Dietary NaCl supplementation prevents muscle necrosis in a mouse model of Duchenne muscular dystrophy.
M. Yoshida, A. Yonetani, T. Shirasaki, and K. Wada (2006)
Am J Physiol Regulatory Integrative Comp Physiol 290, R449-R455
   Abstract »    Full Text »    PDF »
Sustained Whole-Body Functional Rescue in Congestive Heart Failure and Muscular Dystrophy Hamsters by Systemic Gene Transfer.
T. Zhu, L. Zhou, S. Mori, Z. Wang, C. F. McTiernan, C. Qiao, C. Chen, D. W. Wang, J. Li, and X. Xiao (2005)
Circulation 112, 2650-2659
   Abstract »    Full Text »    PDF »
Physiological genomics in PG and beyond: July to September 2005.
M. Liang and B. Ventura (2005)
Physiol Genomics 23, 119-124
   Full Text »    PDF »
Molecular, cellular, and pharmacological therapies for Duchenne/Becker muscular dystrophies.
J. V. Chakkalakal, J. Thompson, R. J. Parks, and B. J. Jasmin (2005)
FASEB J 19, 880-891
   Abstract »    Full Text »    PDF »
In Vivo Fusion of Circulating Fluorescent Cells with Dystrophin-Deficient Myofibers Results in Extensive Sarcoplasmic Fluorescence Expression but Limited Dystrophin Sarcolemmal Expression.
F. Chretien, P. A. Dreyfus, C. Christov, P. Caramelle, J.-L. Lagrange, B. Chazaud, and R. K. Gherardi (2005)
Am. J. Pathol. 166, 1741-1748
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)