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Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs

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Abstract

Our study aimed to target adenoviral gene therapy to the uteroplacental circulation of pregnant guinea pigs in order to develop a novel therapy for fetal growth restriction. Four methods of delivery of an adenovirus encoding β-galactosidase (Ad.LacZ) were evaluated: intravascular injection using phosphate-buffered saline (PBS) into (1) uterine artery (UtA) or (2) internal iliac artery or external administration in (3) PBS or (4) pluronic F-127 gel (Sigma Aldrich). Postmortem examination was performed 4 to 7 days after gene transfer. Tissue transduction was assessed by X-gal histochemistry and enzyme-linked immunosorbent assay. External vascular application of the adenovirus vector in combination with pluronic gel had 91.7% success rate in terms of administration (85% maternal survival) and gave the best results for maternal/fetal survival and local transduction efficiency without any spread to maternal or fetal tissues. This study suggests an optimal method of gene delivery to the UtAs of a small rodent for preclinical studies.

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Authors and Affiliations

  1. Institute for Women’s Health, University College London, London, United Kingdom

    Vedanta Mehta PhD, Keren Ofir MD, Anna Swanson PhD, Ewa Kloczko BSc, Donald Peebles MD, FRCOG & Anna L. David PhD, MRCOG

  2. Centre for Cardiovascular Biology and Medicine, University College London, Rayne Building, 5 University Stree, WC1E 6JF, London, United Kingdom

    Vedanta Mehta PhD, John Martin MD & Ian Zachary PhD

  3. BSU, Royal Veterinary College, London, United Kingdom

    Michael Boyd MSc, Hannah Barker MSc & Adnan Avdic-Belltheus MSc

Authors
  1. Vedanta Mehta PhD
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  2. Keren Ofir MD
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  3. Anna Swanson PhD
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  4. Ewa Kloczko BSc
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  5. Michael Boyd MSc
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  6. Hannah Barker MSc
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  7. Adnan Avdic-Belltheus MSc
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  8. John Martin MD
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  9. Ian Zachary PhD
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  10. Donald Peebles MD, FRCOG
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  11. Anna L. David PhD, MRCOG
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Correspondence to Vedanta Mehta PhD.

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Mehta, V., Ofir, K., Swanson, A. et al. Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs. Reprod. Sci. 23, 1087–1095 (2016). https://doi.org/10.1177/1933719116630411

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  • DOI: https://doi.org/10.1177/1933719116630411

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