ABSTRACT
OBJECTIVE: We sought to determine whether the transfer of enzyme-encoding genes in utero can be detected after birth. STUDY DESIGN: An adenoviral vector carrying the gene for beta-galactosidase was injected under ultrasonographic guidance into the livers of 4 rabbit fetuses per litter (3 litters total) at 27 days' gestation. On delivery of the pups 2 to 3 days later, the livers were analyzed for beta-galactosidase activity by using 5-bromo-4-chloro-3-indolyl-beta-D -galactopyranoside (X-gal) staining. Polymerase chain reaction was also performed on liver extracts as an additional independent measure of successful vector delivery. RESULTS: Successful targeting of the livers of fetal rabbits was demonstrated by beta-galactosidase activity in the nuclei of liver serosal cells, parenchymal hepatocytes, or columnar cells of the gallbladder in 7 (58%) of 12 injected pups and by polymerase chain reaction in liver extracts from 10 (83%) of 12 injected pups. CONCLUSIONS: These results suggest that vectors that carry genes for specific enzymes can be delivered to fetal organs in utero and that expression of the enzyme can be detected after delivery.
