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Perinatal Gene Therapy

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Fetal Stem Cells in Regenerative Medicine

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

The first human gene therapy trials began over 10 years ago, but in spite of continuous technological progress most clinical results have been disappointing. The reasons for this include difficulties in targeting the appropriate organ, a robust immune response to the therapy in adults and low level expression of the therapeutic gene product. Applying the therapy before birth may avoid these difficulties, and recent pre-clinical work has shown proof-of-principle for phenotypic cure of congenital disease in animal models using this approach. Selecting the right diseases for therapeutic intervention will be critical for clinical translation. Perinatal application of gene therapy has been proposed to be appropriate for life-threatening disorders, in which prenatal gene delivery maintains a clear advantage over cell transplantation or postnatal gene therapy and for which there are currently no satisfactory treatments available. Gene therapy could be applied directly to the fetus in utero. In the case of maternal pathology affecting the fetus such as occurs in uteroplacental insufficiency, a major cause of fetal growth restriction, gene therapy could be given to the mother. Combining stem cell transplantation (SCT) and gene therapy by transplanting the fetus with gene corrected autologous stem cells is an attractive proposition. This would avoid some of the issues of safety with regard to direct fetal vector injection, in particular the potential for germline gene transfer and untargeted fetal systemic vector delivery.

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  1. Institute for Women’s Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK

    Panicos Shangaris M.B.B.Ch., B.A.O., M.Sc. & Anna L. David Ph.D., M.R.C.O.G.

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  1. Panicos Shangaris M.B.B.Ch., B.A.O., M.Sc.
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Correspondence to Anna L. David Ph.D., M.R.C.O.G. .

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  1. Department of Surgery, Childrens Hosp Boston & Harvard Med, Boston, Massachusetts, USA

    Dario O. Fauza

  2. Department of Cellular and Molecular Med, University of Ottawa, Faculty of Medicin, OTTAWA, Ontario, Canada

    Mahmud Bani

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Shangaris, P., David, A.L. (2016). Perinatal Gene Therapy. In: Fauza, D., Bani, M. (eds) Fetal Stem Cells in Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3483-6_19

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