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J Clin Invest. 2000 Mar;105(5):589-96.

Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia.

Author information

1
Program in Gene Therapy, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.

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.

PMID:
10712430
PMCID:
PMC292456
DOI:
10.1172/JCI8858
[Indexed for MEDLINE]
Free PMC Article

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