title: Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo.
abstract: 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.
authors.affiliation: Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: M A
authors.initials: MA
authors.lastname: Rosenfeld
authors.forename: W
authors.initials: W
authors.lastname: Siegfried
authors.forename: K
authors.initials: K
authors.lastname: Yoshimura
authors.forename: K
authors.initials: K
authors.lastname: Yoneyama
authors.forename: M
authors.initials: M
authors.lastname: Fukayama
authors.forename: L E
authors.initials: LE
authors.lastname: Stier
authors.forename: P K
authors.initials: PK
authors.lastname: Pääkkö
authors.forename: P
authors.initials: P
authors.lastname: Gilardi
authors.forename: L D
authors.initials: LD
authors.lastname: Stratford-Perricaudet
authors.forename: M
authors.initials: M
authors.lastname: Perricaudet
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D004274:DNA, Recombinant; D004646:Emphysema / Q000235:genetics / Q000628:therapy; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016205:Sigmodontinae; D014132:Trachea / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004274:DNA, Recombinant; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin