Comparative in vivo approaches for selective adenovirus-mediated gene delivery to the placenta.
Gene delivery to the placenta is one potential way of specifically modifying placental biological processes and fetal development. The aim of this study was to determine the most efficient and least invasive route of placental adenovirus delivery. The feasibility of adenovirus-mediated gene transfer to the rat placenta was addressed by maternal intravenous or direct intraplacental injection of adenoviral vectors expressing the glucose transporter GLUT3, a noncirculating integral membrane protein. Both routes led to transgene expression in the placenta. However, direct intraplacental delivery on day 14 of gestation yielded a higher transduction efficiency than maternal intravenous administration, and markedly reduced transgene expression in maternal liver. Most importantly, the amount of the GLUT3 transgene and the adenovirus itself in fetal tissues was only 1 to 3% of that found in the placenta. These results indicate that the nature of the transgene and the route of adenovirus administration are key parameters in selective placental somatic gene transfer. This novel strategy may prove useful for modifying a placental function without altering the fetal genome.
Xing
A
A
CNRS UPR-1524, Meudon, France.
Boileau
P
P
Caüzac
M
M
Challier
J C
JC
Girard
J
J
Hauguel-de Mouzon
S
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D051274:Glucose Transporter Type 3; D006801:Humans; D007275:Injections, Intravenous; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D017931:DNA Primers; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495687:SLC2A3 protein, human; C495690:Slc2a3 protein, rat