title: Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs.
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.
authors: Institute for Women's Health, University College London, London, United Kingdom Centre for Cardiovascular Biology and Medicine, University College London, London, United Kingdom v.mehta@ucl.ac.uk.
authors: Vedanta
authors: V
authors: Mehta
authors: Institute for Women's Health, University College London, London, United Kingdom.
authors: Keren
authors: K
authors: Ofir
authors: Institute for Women's Health, University College London, London, United Kingdom.
authors: Anna
authors: A
authors: Swanson
authors: Institute for Women's Health, University College London, London, United Kingdom.
authors: Ewa
authors: E
authors: Kloczko
authors: BSU, Royal Veterinary College, London, United Kingdom.
authors: Michael
authors: M
authors: Boyd
authors: BSU, Royal Veterinary College, London, United Kingdom.
authors: Hannah
authors: H
authors: Barker
authors: BSU, Royal Veterinary College, London, United Kingdom.
authors: Adnan
authors: A
authors: Avdic-Belltheus
authors: Centre for Cardiovascular Biology and Medicine, University College London, London, United Kingdom.
authors: John
authors: J
authors: Martin
authors: Centre for Cardiovascular Biology and Medicine, University College London, London, United Kingdom.
authors: Ian
authors: I
authors: Zachary
authors: Institute for Women's Health, University College London, London, United Kingdom.
authors: Donald
authors: D
authors: Peebles
authors: Institute for Women's Health, University College London, London, United Kingdom.
authors: Anna L
authors: AL
authors: David
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005317:Fetal Growth Retardation / Q000628:therapy*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006168:Guinea Pigs; D007083:Iliac Artery; D021041:Placental Circulation; D011247:Pregnancy; D017534:Radial Artery; D055988:Uterine Artery; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D001616:beta-Galactosidase
keywords: VEGF-A165; adenovirus vector; guinea pig; pluronic gel; prenatal gene therapy; uteroplacental circulation