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Science 19 April 1991: Vol. 252. no. 5004, pp. 431 - 434 DOI: 10.1126/science.2017680
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Articles
Science, Vol 252, Issue 5004, 431-434
Copyright © 1991 by American Association for the Advancement of Science
Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo
MA Rosenfeld,
W Siegfried,
K Yoshimura,
K Yoneyama,
M Fukayama,
LE Stier,
PK Paakko,
P Gilardi,
LD Stratford-Perricaudet,
M Perricaudet,
and
al. et
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis. A replication-deficient adenoviral vector (Ad-alpha 1AT) containing an adenovirus major late promoter and a recombinant human alpha 1AT gene was used to infect epithelial cells of the cotton rat respiratory tract in vitro and in vivo. Freshly isolated tracheobronchial epithelial cells infected with Ad-alpha 1AT contained human alpha 1AT messenger RNA transcripts and synthesized and secreted human alpha 1AT. After in vivo intratracheal administration of Ad-alpha 1AT to these rats, human alpha 1AT messenger RNA was observed in the respiratory epithelium, human alpha 1AT was synthesized and secreted by lung tissue, and human alpha 1AT was detected in the epithelial lining fluid for at least 1 week.
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