Fetal membranes act as a barrier for adenoviruses: gene transfer into exocoelomic cavity of rat fetuses does not affect cells in the fetus.

Abstract

In utero gene therapy has a potential to correct genetic disorders before the first clinical symptoms appear. Our aim was to examine whether the exocoelomic cavity between amniotic and chorionic membranes offers a minimally invasive route for gene transfer to the fetus during early pregnancy. We injected lacZ-adenovirus (4 x 10(9) pfu) during open surgery into the exocoelomic cavity of rat fetuses (n=50) and analyzed the fetuses and rat dams for transgene expression with X-gal staining and polymerase chain reaction. Giant cells around Reichert's membrane, the outermost extraembryonic membrane in rodents, were transduced; but no transduction was observed in the cells of the fetuses or rat dams. In rodents, the exocoelomic cavity does not offer a route for gene transfer into the fetus. It was concluded that fetal membranes act as a barrier that prevents adenoviral particles from passing between embryonic cavities.