Journal article
A low rate of cell proliferation and reduced DNA uptake limit cationic lipid-mediated gene transfer to primary cultures of ciliated human airway epithelia
Gene therapy, Vol.4(11), pp.1173-1180
1997
DOI: 10.1038/sj.gt.3300524
PMID: 9425440
Abstract
Complexes of DNA and cationic lipid offer potential advantages for gene transfer to airway epithelia. However, we found that application of DNA-lipid (DMRIE-DOPE) complexes to primary cultures of human ciliated airway epithelia or explants of rabbit trachea generated only low levels of gene transfer. In contrast, when we applied the DNA-lipid to immature human epithelia shortly after seeding, transgene expression was substantially higher. We identified two barriers that limit gene transfer. First, uptake of the DNA-lipid complexes into airway cells across the apical membrane decreased rapidly with time after seeding and paralleled the decrease in transgene expression. Second, cell division decreased with time after seeding, and we found that cells in mitosis (labeled with BrdU) were much more likely to express transgene than BrdU-negative cells. These data suggest that the entry step across the apical membrane and the low rate of cell division are important barriers for cationic lipid-mediated gene transfer to airway epithelia. Attempts to modify these two processes may yield improvements in the efficiency of gene transfer to the airways in cystic fibrosis.
Details
- Title: Subtitle
- A low rate of cell proliferation and reduced DNA uptake limit cationic lipid-mediated gene transfer to primary cultures of ciliated human airway epithelia
- Creators
- A FASBENDER - Howard Hughes Medical Institute and Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United StatesJ ZABNER - Howard Hughes Medical Institute and Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United StatesB. G ZEIHER - Howard Hughes Medical Institute and Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United StatesM. J WELSH - Howard Hughes Medical Institute and Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.4(11), pp.1173-1180
- DOI
- 10.1038/sj.gt.3300524
- PMID
- 9425440
- NLM abbreviation
- Gene Ther
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- Nature Publishing Group; Basingstoke
- Language
- English
- Date published
- 1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020609802771
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