Ultrasonographically guided direct gene transfer in utero: successful induction of beta-galactosidase in a rabbit model.
OBJECTIVE
We sought to determine whether the transfer of enzyme-encoding genes in utero can be detected after birth.


METHODS
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.
Baumgartner
T L
TL
Department of Obstetrics, University of Texas Health Science Center at Houston, Division of Neurosurgery, Houston, Texas, USA.
Baumgartner
B J
BJ
Hudon
L
L
Moise
K J
KJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002863:Chromogenic Compounds / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D005697:Galactosides / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005865:Gestational Age; D006367:HeLa Cells / Q000201:enzymology; D006651:Histocytochemistry; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008099:Liver / Q000196:embryology* / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011817:Rabbits; D014463:Ultrasonography; D001616:beta-Galactosidase / Q000235:genetics*
D002863:Chromogenic Compounds; D005697:Galactosides; D007211:Indoles; D001616:beta-Galactosidase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside