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

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

doi:10.1172/JCI8858

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

Journal article

Open access

Peer reviewed

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

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

The Journal of clinical investigation, Vol.105(5), pp.589-596

03/01/2000

DOI: 10.1172/JCI8858

PMCID: PMC292456

PMID: 10712430

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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.

Details

Title: Subtitle: Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia
Creators: Paola T Drapkin - Program in Gene Therapy
Catherine R O’Riordan - Program in Gene Therapy
Su Min Yi - Program in Gene Therapy
John A Chiorini - Program in Gene Therapy
Jonathan Cardella - Program in Gene Therapy
Joseph Zabner - Program in Gene Therapy
Michael J Welsh - Program in Gene Therapy
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.105(5), pp.589-596
Publisher: American Society for Clinical Investigation
DOI: 10.1172/JCI8858
PMID: 10712430
PMCID: PMC292456
ISSN: 0021-9738
eISSN: 1558-8238
Language: English
Date published: 03/01/2000
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
Record Identifier: 9984020613702771

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