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Animal Models for Prenatal Gene Therapy: The Nonhuman Primate Model

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Book cover Prenatal Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 891))

Abstract

Intrauterine gene therapy (IUGT) potentially enables the treatment and possible cure of monogenic ­diseases that cause severe fetal damage. The main benefits of this approach will be the ability to correct the disorder before the onset of irreversible pathology and inducing central immune tolerance to the vector and transgene if treatment is instituted in early gestation. Cure has been demonstrated in small animal models, but because of the significant differences in immune ontogeny and the much shorter gestation compared to humans, it is unlikely that questions of long-term efficacy and safety will be adequately addressed in rodents. The nonhuman primate (NHP) allows investigation of key issues, in particular, the different outcomes in early and late-gestation IUGT associated with different stages of immune maturity, longevity of transgene expression, and delayed-onset adverse events in treated offspring and mothers including insertional mutagenesis. Here, we describe a model based on the Macaca fascicularis using ultrasound and fetoscopic approaches to systemic vector delivery and the processes involved in vector administration and longitudinal analyses.

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Author information

Authors and Affiliations

  1. Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, Singapore, Singapore

    Citra N. Mattar, Arijit Biswas, Mahesh Choolani & Jerry K. Y. Chan MD, PhD

  2. Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Jerry K. Y. Chan MD, PhD

  3. Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore

    Jerry K. Y. Chan MD, PhD

Authors
  1. Citra N. Mattar
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  2. Arijit Biswas
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  3. Mahesh Choolani
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  4. Jerry K. Y. Chan MD, PhD
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Corresponding author

Correspondence to Jerry K. Y. Chan MD, PhD .

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Editors and Affiliations

  1. National Heart & Lung Inst., Molecular & Cellular Medicine Sec., Imperial College London, Imperial College Road, London, SW7 2AZ, United Kingdom

    Charles Coutelle

  2. Reader in Gene Transfer Technology, Gene Transfer Technology Group, University College London, Chenies Mews 86-96, London, WC1E 6HX, United Kingdom

    Simon N. Waddington

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Mattar, C.N., Biswas, A., Choolani, M., Chan, J.K.Y. (2012). Animal Models for Prenatal Gene Therapy: The Nonhuman Primate Model. In: Coutelle, C., Waddington, S. (eds) Prenatal Gene Therapy. Methods in Molecular Biology, vol 891. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-873-3_12

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  • DOI: https://doi.org/10.1007/978-1-61779-873-3_12

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-872-6

  • Online ISBN: 978-1-61779-873-3

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