Journal article
Mechanism by which calcium phosphate coprecipitation enhances adenovirus-mediated gene transfer
Gene therapy, Vol.6(11), pp.1845-1850
1999
DOI: 10.1038/sj.gt.3301020
PMID: 10602380
Abstract
Delivery of a normal copy of CFTR cDNA to airway epithelia may provide a novel treatment for cystic fibrosis lung disease. Unfortunately, current vectors are inefficient because of limited binding to the apical surface of airway epithelia. We recently reported that incorporation of adenovirus in a calcium phosphate coprecipitate (Ad:CaPi) improves adenovirus-mediated gene transfer to airway epithelia in vitro and in vivo. To understand better how coprecipitation improves gene transfer, we tested the hypothesis that incorporation in a CaPi coprecipitate increases the binding of adenovirus to the apical surface of differentiated human airway epithelia. When a Cy3-labelled adenovirus was delivered in a coprecipitate, binding increased 54-fold as compared with adenovirus alone. Moreover, infection by Ad:CaPi was independent of fiber knob-CAR and penton base-integrin interactions. After binding to the cell surface, the virus must enter the cell in order to infect. We hypothesized that Ad:CaPi may stimulate fluid phase endocytosis, thereby facilitating entry. However, we found that neither adenovirus nor Ad:CaPi coprecipitates altered fluid phase endocytosis. Nevertheless, Ad:CaPi preferentially infected cells showing endocytosis. Thus, CaPi coprecipitation improves adenovirus-mediated gene transfer by coating the epithelial surface with a layer of virus which enters cells during the normal process of endocytosis.
Details
- Title: Subtitle
- Mechanism by which calcium phosphate coprecipitation enhances adenovirus-mediated gene transfer
- Creators
- R. W WALTERS - Howard Hughes Medical Institute, 500 EMRB, Program in Gene Therapy, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, United StatesM. J WELSH - Howard Hughes Medical Institute, 500 EMRB, Program in Gene Therapy, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.6(11), pp.1845-1850
- Publisher
- Nature Publishing Group; Basingstoke
- DOI
- 10.1038/sj.gt.3301020
- PMID
- 10602380
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Language
- English
- Date published
- 1999
- 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
- 9984014595402771
Metrics
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