Journal article
Adenoviral-mediated gene transfer to fetal pulmonary epithelia in vitro and in vivo
The Journal of clinical investigation, Vol.95(6), pp.2620-2632
06/1995
DOI: 10.1172/JCI117964
PMCID: PMC295945
PMID: 7539457
Abstract
Vector-mediated gene transfer offers a direct method of correcting genetic pulmonary diseases and might also be used to correct temporary abnormalities associated with acquired, nongenetic disorders. Because the fetus or newborn may be a more immune tolerant host for gene transfer using viral vectors, we used replication defective recombinant adenoviral vectors to test the feasibility of gene transfer to the fetal pulmonary epithelium in vitro and in vivo. Both proximal and distal epithelial cells in cultured fetal lung tissues from rodents and humans diffusely expressed the lacZ transgene 3 d after viral infection. In vivo gene delivery experiments were performed in fetal mice and lambs. Delivery of Ad2/CMV-beta Gal to the amniotic fluid in mice produced intense transgene expression in the fetal epidermis and amniotic membranes, some gastrointestinal expression, but no significant airway epithelial expression. When we introduced the adenoviral vector directly into the trachea of fetal lambs, the lacZ gene was expressed in the tracheal, bronchial, and distal pulmonary epithelial cells 3 d after viral infection. Unexpectedly, reactive hyperplasia and squamous metaplasia were noted in epithelia expressing lacZ in the trachea, but not in the distal lung of fetal lambs. 1 wk after infection, adenovirus-treated fetuses developed inflammatory cell infiltrates in the lung tissue with CD4, CD8, IgM, and granulocyte/macrophage positive immune effector cells. Transgene expression faded coincident with inflammation and serologic evidence of antiadenoviral antibody production. While these studies document the feasibility of viral-mediated gene transfer in the prenatal lung, they indicate that immunologic responses to E1-deleted recombinant adenoviruses limit the duration of transgene expression.
Details
- Title: Subtitle
- Adenoviral-mediated gene transfer to fetal pulmonary epithelia in vitro and in vivo
- Creators
- Paul B McCray Jr - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAKelly Armstrong - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAJoseph Zabner - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USADaniel W Miller - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAGary A Koretzky - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USALarry Couture - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAJean E Robillard - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAAlan E Smith - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USAMichael J Welsh - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.95(6), pp.2620-2632
- DOI
- 10.1172/JCI117964
- PMID
- 7539457
- PMCID
- PMC295945
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 06/1995
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Neurosurgery; Medicine Administration; Internal Medicine
- Record Identifier
- 9984020756602771
Metrics
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