FETAL GENE DELIVERY IN MICE BY INTRAAMNIOTIC ADMINISTRATION OF RETROVIRAL PRODUCER CELLS AND ADENOVIRUS

With the aim of developing foetal gene therapy for cystic fibrosis, we have investigated the possibility of gene targeting to the mouse foet us with two different viral vector systems and at different times of g estation. We report here that recombinant retrovirus producing cells a dministered into the intra-amniotic cavity of mid- to late-gestation m ouse MF1 foetuses survive in the amniotic fluid and are able to engraf t to a certain extent in foetal tissues. By production of infectious v irus they mediate transduction and beta-galactosidase transgene expres sion in neighbouring foetal tissues 24 to 72 h following injection. Re trovirus producer cells could, therefore become a means to overcome th e limitations of low retroviral titre, for in vivo foetal gene transfe r To investigate the developmental stage at which transduction of the airways and enteral systems can be obtained we also administered a hig hly infective first generation adenoviral vector (AdRSV beta gal) into the amniotic cavity of foetal mice between 13 to 16 days post coitus. beta-galactosidase activity was detected between 24 to 120 h after in jection. The highest levels of transgene expression were generally obs erved between 48 to 72 h following injection of the adenoviral vector. We demonstrate that infection of the pulmonary airways is dependent o n the developmental stage of the foetus and can be achieved on the 15t h day of gestation.