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Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia
Paola T. Drapkin, … , Joseph Zabner, Michael J. Welsh
Paola T. Drapkin, … , Joseph Zabner, Michael J. Welsh
Published March 1, 2000
Citation Information: J Clin Invest. 2000;105(5):589-596. https://doi.org/10.1172/JCI8858.
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Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia

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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.

Authors

Paola T. Drapkin, Catherine R. O’Riordan, Su Min Yi, John A. Chiorini, Jonathan Cardella, Joseph Zabner, Michael J. Welsh

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Figure 4

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Apical fluid-phase endocytosis by human airway epithelia stimulated by u...
Apical fluid-phase endocytosis by human airway epithelia stimulated by uPA and u7-peptide. Data are en face images showing Texas red–labeled dextran uptake. Shown are basal endocytosis (a), endocytosis after apical application of 50 nM uPA (b), 0.15 μM u7-peptide (c), or 0.15 μM scrambled u7-peptide (d), effect of uPA and peptides on number of cells showing endocytosis (e). n = 5, *P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 8 patents
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