Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia
Open Access
- 1 March 2000
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 105 (5) , 589-596
- https://doi.org/10.1172/jci8858
Abstract
Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adeno-associated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia.Keywords
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