Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs

Vedanta Mehta; Keren Ofir; Anna Swanson; Ewa Kloczko; Michael Boyd; Hannah Barker; Adnan Avdic-Belltheus; John Martin; Ian Zachary; Donald Peebles; Anna L. David

doi:10.1177/1933719116630411

Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs

Vedanta Mehta^*, Keren Ofir, Anna Swanson, Ewa Kloczko, Michael Boyd, Hannah Barker, Adnan Avdic-Belltheus, John Martin, Ian Zachary, Donald Peebles, Anna L. David

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	1087-1095
Number of pages	9
Journal	Reproductive Sciences
Volume	23
Issue number	8
DOIs	https://doi.org/10.1177/1933719116630411
State	Published - 1 Aug 2016
Externally published	Yes

Keywords

Guinea pig
VEGF-A
adenovirus vector
pluronic gel
prenatal gene therapy
uteroplacental circulation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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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AU - Barker, Hannah

AU - Avdic-Belltheus, Adnan

AU - Martin, John

AU - Zachary, Ian

AU - Peebles, Donald

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Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs

Abstract

Keywords

UN SDGs

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