Journal article
In vivo retroviral gene transfer into human bronchial epithelia of xenografts
The Journal of clinical investigation, Vol.90(6), pp.2598-2607
12/01/1992
DOI: 10.1172/JCI116155
PMCID: PMC443420
PMID: 1281842
Abstract
Cystic fibrosis (CF) is the most common lethal inherited disease in the Caucasian population with an incidence of approximately 1 in 2,500 live births. Pulmonary complications of CF, which are the most morbid aspects of the disease, are caused by primary abnormalities in epithelial cells that lead to impaired mucociliary clearance. One potential therapeutic strategy is to reconstitute expression of the CF gene in airway epithelia by somatic gene transfer. To this end, we have developed an animal model of the human airway using bronchial xenografts and have tested the efficiency of in vivo retroviral gene transfer. Using the LacZ reporter gene, we find the efficiency of in vivo retroviral gene transfer to be dramatically dependent on the regenerative and mitotic state of the epithelium. Within an undifferentiated regenerating epithelium in which 40% of nuclei labeled with BrdU, 5-10% retroviral gene transfer was obtained. In contrast, no gene transfer was noted in a fully differentiated epithelium in which 1% of nuclei labeled with BrdU. These findings suggest that retroviral mediated gene transfer to the airway in vivo may be feasible if the proper regenerative state can be induced.
Details
- Title: Subtitle
- In vivo retroviral gene transfer into human bronchial epithelia of xenografts
- Creators
- J F Engelhardt - University of Michigan–Ann ArborJ R Yankaskas - University of Michigan–Ann ArborJ M Wilson - University of Michigan–Ann Arbor
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.90(6), pp.2598-2607
- DOI
- 10.1172/JCI116155
- PMID
- 1281842
- PMCID
- PMC443420
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 12/01/1992
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284355602771
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