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Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs

Mehta, V; Ofir, K; Swanson, A; Kloczko, E; Boyd, M; Barker, H; Avdic-Belltheus, A; ... David, AL; + view all (2016) Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs. Reproductive Sciences , 23 (8) pp. 1087-1095. 10.1177/1933719116630411. Green open access

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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.

Type: Article
Title: Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/1933719116630411
Publisher version: https://doi.org/10.1177%2F1933719116630411
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: prenatal gene therapy, uteroplacental circulation, guinea pig, adenovirus vector, pluronic gel, VEGF-A165
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/10066736
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