Comparative in vivo approaches for selective adenovirus-mediated gene delivery to the placenta

Gene delivery to the placenta is one potential way of specifically modifyin g placental biological processes and fetal development, The aim of this stu dy was to determine the most efficient and least invasive route of placenta l adenovirus delivery, The feasibility of adenovirus-mediated gene transfer to the rat placenta was addressed by maternal intravenous or direct intrap lacental injection of adenoviral vectors expressing the glucose transporter GLUT3, a noncirculating integral membrane protein. Both routes led to tran sgene expression in the placenta. However, direct intraplacental delivery o n day 14 of gestation yielded a higher transduction efficiency than materna l intravenous administration, and markedly reduced transgene expression in maternal liver, Most importantly, the amount of the GLUT3 transgene and the adenovirus itself in fetal tissues was only 1 to 3% of that found in the p lacenta. These results indicate that the nature of the transgene and the ro ute of adenovirus administration are key parameters in selective placental somatic gene transfer. This novel strategy may prove useful for modifying a placental function without altering the fetal genome.