Journal article
Influence of Cell Polarity on Retrovirus-Mediated Gene Transfer to Differentiated Human Airway Epithelia
Journal of virology, Vol.72(12), pp.9818-9826
12/1998
DOI: 10.1128/JVI.72.12.9818-9826.1998
PMCID: PMC110493
PMID: 9811717
Abstract
Gene transfer with recombinant murine leukemia viruses (MuLV) provides the potential to permanently correct inherited lung diseases, such as cystic fibrosis (CF). Several problems prevent the application of MuLV-based recombinant retroviruses to lung gene therapy: (i) the lack of cell proliferation in mature pulmonary epithelia, (ii) inefficient gene transfer with a vector applied to the apical surface, and (iii) low titers of many retroviral preparations. We found that keratinocyte growth factor (KGF) stimulated proliferation of differentiated human tracheal and bronchial epithelia. Approximately 50% of epithelia divided in response to KGF as assessed by bromodeoxyuridine histochemistry. In airway epithelia stimulated to divide with KGF, high-titer ampho- and xenotropic enveloped vectors preferentially infected cells from the basal side. However, treatment with hypotonic shock or EGTA transiently increased transepithelial permeability, enhancing gene transfer with the vector applied to the mucosal surfaces of KGF-stimulated epithelia. Up to 35% of cells expressed the transgene after gene transfer. By using this approach, cells throughout the epithelial sheet, including basal cells, were targeted. Moreover, the Cl
−
transport defect in differentiated CF airway epithelia was corrected. These findings suggest that barriers to apical infection with MuLV can be overcome.
Details
- Title: Subtitle
- Influence of Cell Polarity on Retrovirus-Mediated Gene Transfer to Differentiated Human Airway Epithelia
- Creators
- Guoshun Wang - Departments of PediatricsBeverly L Davidson - Departments of PediatricsPaul Melchert - Departments of PediatricsVladimir A Slepushkin - Departments of PediatricsHelmuth H. G van Es - Departments of PediatricsMordechai Bodner - Departments of PediatricsDoug J Jolly - Departments of PediatricsPaul B McCray - Departments of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.72(12), pp.9818-9826
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.72.12.9818-9826.1998
- PMID
- 9811717
- PMCID
- PMC110493
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 12/1998
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093318702771
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