Submit a comment

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
Paola T. Drapkin, Catherine R. O’Riordan, Su Min Yi, John A. Chiorini, Jonathan Cardella, Joseph Zabner, Michael J. Welsh
View: Text | PDF
Article

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

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

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required