American Journal of Obstetrics & Gynecology
Volume 193, Issue 3, Supplement , Pages 1105-1109 , September 2005

Targeting the respiratory muscles of fetal sheep for prenatal gene therapy for Duchenne muscular dystrophy

  • Boaz Weisz, MD

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London
    • Corresponding Author InformationReprint requests: Dr Boaz Weisz, Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, WC1E6HX, London, UK.
    • ,
  • Anna L. David, MD

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London
    • ,
  • Lisa G. Gregory, PhD

      Affiliations

    • Imperial College of Science, Technology and Medicine, University of London, Section of Molecular Genetics, Gene Therapy Research Group
    • ,
  • Dany Perocheau, BSc

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London
    • ,
  • Ali Ruthe, BSc

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London
    • ,
  • Simon N. Waddington, PhD

      Affiliations

    • Imperial College of Science, Technology and Medicine, University of London, Section of Molecular Genetics, Gene Therapy Research Group
    • ,
  • Mike Themis, PhD

      Affiliations

    • Imperial College of Science, Technology and Medicine, University of London, Section of Molecular Genetics, Gene Therapy Research Group
    • ,
  • Terry Cook, MD

      Affiliations

    • Department of Histopathology, Imperial College of Science, Technology and Medicine, University of London, London, United Kingdom
    • ,
  • Charles Coutelle, PhD

      Affiliations

    • Imperial College of Science, Technology and Medicine, University of London, Section of Molecular Genetics, Gene Therapy Research Group
    • ,
  • Charles H. Rodeck, MD

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London
    • ,
  • Donald M. Peebles, MD

      Affiliations

    • Department of Obstetrics and Gynaecology, University College London

Received 24 February 2005 ,Revised 29 April 2005 ,Accepted 26 May 2005.

References 

  1. Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987;50:509–517
  2. Emery Alan EH. Duchenne muscular dystrophy. Oxford: Oxford University Press; 1993;
  3. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Chest. 1997;112:1024–1028
  4. van Deutekom JC, van Ommen GJ. Advances in Duchenne muscular dystrophy gene therapy. Nat Rev Genet. 2003;4:774–783
  5. Wells DJ, Wells KE. Gene transfer studies in animals: what do they really tell us about the prospects for gene therapy in DMD?. Neuromuscul Disord. 2002;12(Suppl 1):S11–S22
  6. Acsadi G, Dickson G, Love DR, Jani A, Walsh FS, Gurusinghe A, et al. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature. 1991;352:815–818
  7. Wells DJ, Ferrer A, Wells KE. Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy. Expert Rev Mol Med. 2002;2002:1–23
  8. Wells DJ, Wells KE, Asante EA, Turner G, Sunada Y, Campbell KP, et al. Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy. Hum Mol Genet. 1995;4:1245–1250
  9. Ferrer A, Wells KE, Wells DJ. Immune responses to dystropin: implications for gene therapy of Duchenne muscular dystrophy. Gene Ther. 2000;7:1439–1446
  10. Braun S, Thioudellet C, Rodriguez P, Ali-Hadji D, Perraud F, Accart N, et al. Immune rejection of human dystrophin following intramuscular injections of naked DNA in mdx mice. Gene Ther. 2000;7:1447–1457
  11. Ahmad A, Brinson M, Hodges BL, Chamberlain JS, Amalfitano A. Mdx mice inducibly expressing dystrophin provide insights into the potential of gene therapy for Duchenne muscular dystrophy. Hum Mol Genet. 2000;9:2507–2515
  12. Waddington SN, Buckley SM, Nivsarkar M, Jezzard S, Schneider H, Dahse T, et al. In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor. Blood. 2003;101:1359–1366
  13. Vassilopoulos D, Emery AE, Gordon N. Nuclear changes in cultured human dystrophic muscle. Experientia. 1977;33:759–760
  14. Emery AE, McGregor L. The foetus in Duchenne muscular dystrophy: muscle growth in tissue culture. Clin Genet. 1977;12:183–187
  15. Emery AE. Muscle histology and creatine kinase levels in the foetus in Duchenne muscular dystrophy. Nature. 1977;266:472–473
  16. Themis M, Schneider H, Kiserud T, Cook T, Adebakin S, Jezzard S, et al. Successful expression of beta-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein. Gene Ther. 1999;6:1239–1248
  17. Peebles D, Gregory LG, David A, Themis M, Waddington SN, Knapton HJ, et al. Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero. Gene Ther. 2004;11:70–78
  18. Gregory LG, Harbottle RP, Lawrence L, Knapton HJ, Themis M, Coutelle C. Enhancement of adenovirus-mediated gene transfer to the airways by DEAE dextran and sodium caprate in vivo. Mol Ther. 2003;7:19–26
  19. David A, Cook T, Waddington S, Peebles D, Nivsarkar M, Knapton H, et al. Ultrasound-guided percutaneous delivery of adenoviral vectors encoding the beta-galactosidase and human factor IX genes to early gestation fetal sheep in utero. Hum Gene Ther. 2003;14:353–364
  20. David AL, Peebles DM, Gregory L, Themis M, Cook T, Coutelle C, et al. Percutaneous ultrasound-guided injection of the trachea in fetal sheep: a novel technique to target the fetal airways. Fetal Diagn Ther. 2003;18:385–390
  21. David AL. Development of ultrasound-guided gene therapy to the sheep fetus. University College London. Thesis/Dissertation; 2004.
  22. Gregory LG, Waddington SN, Holder MV, Mitrophanous KA, Buckley SM, Mosley KL, et al. Highly efficient EIAV-mediated in utero gene transfer and expression in the major muscle groups affected by Duchenne muscular dystrophy. Gene Ther. 2004;11:1117–1125
  23. Waddington SN, Nivsarkar MS, Mistry AR, Buckley SM, Kemball-Cook G, Mosley KL, et al. Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy. Blood. 2004;104:2714–2721
  24. Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med. 2004;10:828–834
  25. Yang EY, Cass DL, Sylvester KG, Wilson JM, Adzick NS. BAPS Prize–1997. Fetal gene therapy: efficacy, toxicity, and immunologic effects of early gestation recombinant adenovirus. British Association of Paediatric Surgeons. J Pediatr Surg. 1999;34:235–241

 Presented at the Twenty-Fifth Annual Meeting of the Society for Maternal Fetal Medicine, February 7-12, 2005, Reno, Nev.

PII: S0002-9378(05)00980-4

doi: 10.1016/j.ajog.2005.06.077

American Journal of Obstetrics & Gynecology
Volume 193, Issue 3, Supplement , Pages 1105-1109 , September 2005

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