Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs.

Authors :: Mehta V
Ofir K
Swanson A
Kloczko E
Boyd M
Barker H
Avdic-Belltheus A
Martin J
Zachary I
Peebles D
David AL
Source :: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2016 Aug; Vol. 23 (8), pp. 1087-95. Date of Electronic Publication: 2016 Feb 10.
Publication Year :: 2016
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.<br /> (© The Author(s) 2016.)