Ultrasonographically guided direct gene transfer in utero: Successful induction of β-galactosidase in a rabbit model

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 β-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 β-galactosidase activity by using 5-bromo-4-chloro-3-indolyl-β-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 β-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. (Am J Obstet Gynecol 1999;181:848-52.)