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

Drapkin PT, ORiordan CR, Yi SM, Chiorini JA, Cardella J, Zabner J, Welsh MJJ Clin Invest2000 03, 105: 5, 589-96

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.

SOTO | USA > SOT Literature > Cystic Fibrosis > Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia.

Editor Recommends
Most Read Articles

Editor Recommends

This SOT Literature Page and all its contents herein are published by SOTO-USA solely for the purpose of education. All rights reserved by SOTO-USA to accept, reject or modify any submission for publication. The opinions stated in the electronically printed material herein are those of the authors and do not necessarily represent the opinions of SOTO-USA or other individuals associated with SOTO-USA. SOTO-USA does not guarantee or make any representation that the printed material contained herein is valid, reliable or accurate. SOTO-USA does not assume any responsibility for injury arising from any use or misuse of the printed material herein. The printed material contained herein is assumed to be from reliable sources and there is no implication that the printed material herein present the only, or the best methodologies or procedures for the care or treatment of conditions discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and treatment information contained herein, and to make modifications as new information and/or research arises.