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 journalArticlepeer-review

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 languageEnglish
Pages (from-to)1087-1095
Number of pages9
JournalReproductive Sciences
Volume23
Issue number8
DOIs
StatePublished - 1 Aug 2016
Externally publishedYes

Keywords

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

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