ADENOVIRUS-MEDIATED TRANSFER OF A RECOMBINANT ALPHA-L-ANTITRYPSIN GENE TO THE LUNG EPITHELIUM INVIVO

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.