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Published ahead of print on February 4, 2005, doi:10.1165/rcmb.2004-0410OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 5, May 2005, 404-410

A more recent version of this article appeared on May 1, 2005
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Submitted on December 23, 2004
Revised on February 2, 2005

Viscoelastic gel formulations enhance airway epithelial gene transfer with viral vectors

Patrick L Sinn1, Ankur J Shah2, Maureen D Donovan2, and Paul B McCray1*

1 Department of Pediatrics, The University of Iowa, Iowa City, IA, USA, 2 Division of Pharmaceutics, The University of Iowa, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: paul-mccray{at}uiowa.edu.

Advances in gene transfer to the conducting airways for the treatment of pulmonary diseases such as cystic fibrosis have identified several vector classes that transduce airway epithelia in vitro and in animal models. One barrier to epithelial gene transfer is the rapid removal of materials from the airway surface via mucociliary clearance. This host defense mechanism limits gene transfer efficiency to airway epithelial cells. Here we show that formulation of gene transfer vectors with viscoelastic gels provides longer epithelial residence time and increases vector-mediated gene transfer efficiency. Gene transfer with adenoviral, adeno-associated, and lentiviral vectors all significantly improved following formulation with viscoelastic gels designed to slow mucociliary clearance. Importantly, viscoelastic gels formulations enhanced vector transduction to the conducting airways, the desired treatment target for diseases such as cystic fibrosis.




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P. L. Sinn, E. R. Burnight, M. A. Hickey, G. W. Blissard, and P. B. McCray Jr.
Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer
J. Virol., October 15, 2005; 79(20): 12818 - 12827.
[Abstract] [Full Text] [PDF]




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