[Expression in vivo of the lacZ gene, delivered to mouse lungs using synthetic microspheres].
A capacity of MF-2 synthetic microspheres to serve as the vehicle for transfer of the marker LacZ gene to mouse lung epithelial cells was studied after a single intranasal administration of the MF-2/gene complex. Two types of plasmids carrying marker gene LacZ were used in the experiments: with cytoplasmic (pCMV-LacZ) and nuclear (pCMV-nlsLacZ) localization of the gene product (beta-galactosidase). As early as 7 days after the complexes MF-2/pCMV-LacZ and MF-2/pCMV-nlsLacZ were administered, specific staining for beta-galactosidase revealed this enzyme activity in the epithelial cells of bronchi, bronchioli, and alveoli. The maximum in vivo of the marker gene in the MF-2/pCMV-LacZ complex was observed at day 14 to 21 after administration and the corresponding gene product was detected during the following two months. The MF-2-mediated gene transfer led to a twofold increase in beta-galactosidase activity relative to the case when the "unbound" pCMV-LacZ plasmid was administered. These results suggest that the synthetic microsphere-mediated transfer of alien genes to the lung of experimental animals is promising. Microspheres may be used in gene therapy for pulmonary affections, in particular cystic fibrosis.
Glazkov
P B
PB
Ott Research Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Ivashchenko
T E
TE
Sabetskiĭ
V A
VA
Scholte
B
B
BaranovVS
D000281:Administration, Intranasal; D000818:Animals; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D005819:Genetic Markers; D015316:Genetic Therapy; D005822:Genetic Vectors; D007763:Lac Operon; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008863:Microspheres; D010957:Plasmids; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; D001616:beta-Galactosidase
Ekspressiia in vivo gena lacZ, dostavlennogo v legkie mysheĭ pri pomoshchi sinteticheskikh mikrosfer.