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An important step on the long path to clinical application of in utero gene therapy

Gene Therapy volume 25, pages 451–453 (2018)Cite this article

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When the first concepts of fetal (in utero, prenatal) gene therapy for genetic diseases emerged about 20 odd years ago [1], it seemed that this approach could overcome many of the difficulties that had plagued the gene therapy community since its beginnings in the late 1980s. These problems were, in particular, poor vector delivery, inefficient and only transient gene transfer and low vector titres, as well as immune reactions against vector and therapeutic protein.

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References

  1. Coutelle C, Douar A-M, College WH, Froster U. The challenge of fetal gene therapy. Nat Med. 1995;1:864–6.

    Article  CAS  Google Scholar 

  2. Waddington SN, Kennea NL, Buckley SM, Gregory LG, Themis M, Coutelle C. Fetal and neonatal gene therapy: benefits and pitfalls. Gene Ther. 2004;11 Suppl 1:S92–7.

    Article  CAS  Google Scholar 

  3. David AL, Themis M, Waddington S, Gregory L, Buckley S, Nivsarkar M, et al. The current status and future direction of fetal gene therapy. Gene Ther Mol Biol. 2003;7:181–209.

    Google Scholar 

  4. Coutelle C, Themis M, Waddington SN, Buckley SM, Gregory LG, Nivsarkar MS, et al. Gene therapy progress and prospects: fetal gene therapy - first proofs of concept- some adverse effects. Gene Ther. 2005;12:1601–7.

    Article  CAS  Google Scholar 

  5. Waddington S, Nivsarkar M, Mistry A, Buckley SMK, Al-Allaf F, Bigger, et al. Permanent phenotypic correction of Haemophilia B in immunocompetent mice by prenatal gene therapy. Blood. 2004;104:2714–21.

    Article  CAS  Google Scholar 

  6. Themis M, Waddington SN, Schmidt M, von Kalle C, Wang Y, Al-Allaf F. Oncogenesis following delivery of a non-primate lentiviral gene therapy vector to fetal mice. Mol Ther. 2005;12:763–71.

    Article  CAS  Google Scholar 

  7. Mattar CN, Nathwani AC, Waddington SN, Dighe N, Kaeppe C, Nowrouzi A, et al. Stable human FIX expression after 0.9G intrauterine gene transfer of self-complementary adeno-associated viral vector 5 and 8 in macaques. Mol Ther. 2011;19:1950–60.

    Article  CAS  Google Scholar 

  8. Almeida-Porada G, Atala A, Porada CD. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application. Mol Ther Methods Clin Dev. 2016;5:16020.

    Article  Google Scholar 

  9. David AL. Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction. Placenta. 2017;59 Suppl 1:S44–S50.

    Article  CAS  Google Scholar 

  10. Massaro G, Mattar CNZ, Wong AMS, Sirka E, Buckley SMK, Herbert BR. et al.Fetal gene therapy for neurodegenerative disease of infants.Nat Med. 2018;24:1317–23.

    Article  CAS  Google Scholar 

  11. Mignot C, Gelot A, Bessières B, Daffos F, Voyer M, Menez F, et al. Perinatal-Lethal Gaucher disease. Am J Med Genet. 2003;120A:338–44.

    Article  CAS  Google Scholar 

  12. Coutelle C, Ashcroft R. Risks, benefits and ethical, legal, and societal considerations for translation of prenatal gene therapy to human application. Methods Mol Biol. 2012;891:371–87.

    CAS  Google Scholar 

  13. Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, et al. Prenatal correction of X-linked hypohidrotic ectodermal dysplasia. N Engl J Med. 2018;378:1604–10.

    Article  CAS  Google Scholar 

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  1. National Heart and Lung Institute, Faculty of Medicine, Sir Alexander Fleming Building, London, SW7 2AZ, UK

    Charles Coutelle

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  1. Charles Coutelle
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Correspondence to Charles Coutelle.

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Coutelle, C. An important step on the long path to clinical application of in utero gene therapy. Gene Ther 25, 451–453 (2018). https://doi.org/10.1038/s41434-018-0046-3

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  • DOI: https://doi.org/10.1038/s41434-018-0046-3

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