Adenovirus-mediated gene transfer to the peritoneum and hepatic parenchyma of fetal mice in utero

Background. The development of effective gene transfer in utero will provide alternative approaches to the treatment of genetic disorders. For many disorders, the fetal liver and peritoneum are important target tissues. Our goals were to compare the tissue sites and duration of transferred gene expression after intraperitoneal (IP) or intrahepatic adenoviral-mediated gene transfer in utero in the developing murine fetus. Methods. Dq 15 CD-I fetuses were injected intrahepatically or intraperitoneally with recombinant adenoviruses containing the luciferase or beta-galactosidase reporter gene. Tissue levels of luciferase were quantitated or tissues were examined for X-gal staining. Results, Luciferase expression was observed in multiple fetal tissues (including brain, intestine, liver and lung) and persisted up to 32 days after intrahepatic delivery. Significant hepatic tropism was demonstrated. Conclusions, Intrahepatic and intraperitoneal injection utero results in transduction of multiple tissues in the developing murine fetus. Transuterine Injection of fetal mice via intrahepatic and intraperitoneal routes provides a valuable model for assessing the efficacy of gene delivery vectors in the prenatal treatment of genetic disorders. These studies demonstrate that hepatic and intraperitoneal gene transfer to the developing murine fetus is feasible and may provide therapeutic levels of proteins development.