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

Background. The development of effective gene transfer in utero will provid e alternative approaches to the treatment of genetic disorders. For many di sorders, the fetal liver and peritoneum are important target tissues. Our g oals were to compare the tissue sites and duration of transferred gene expr ession 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 intraperitone ally with recombinant adenoviruses containing the luciferase or beta-galact osidase reporter gene. Tissue levels of luciferase were quantitated or tiss ues were examined for X-gal staining. Results, Luciferase expression was observed in multiple fetal tissues (incl uding brain, intestine, liver and lung) and persisted up to 32 days after i ntrahepatic delivery. Significant hepatic tropism was demonstrated. Conclusions, Intrahepatic and intraperitoneal injection utero results in tr ansduction of multiple tissues in the developing murine fetus. Transuterine Injection of fetal mice via intrahepatic and intraperitoneal routes provid es 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 i s feasible and may provide therapeutic levels of proteins development.