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Published ahead of print on February 4, 2005, doi:10.1165/rcmb.2004-0410OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 404-410, 2005
© 2005 American Thoracic Society
DOI: 10.1165/rcmb.2004-0410OC

Viscoelastic Gel Formulations Enhance Airway Epithelial Gene Transfer with Viral Vectors

Patrick L. Sinn, Ankur J. Shah, Maureen D. Donovan and Paul B. McCray, Jr.

Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa; and Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to Paul B. McCray, Jr., Department of Pediatrics, 240G EMRB, The University of Iowa, Iowa City, IA 52242. 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 after formulation with viscoelastic gels designed to slow mucociliary clearance. Importantly, viscoelastic gel formulations enhanced vector transduction to the conducting airways, the desired treatment target for diseases such as cystic fibrosis.

Key Words: gene transfer • viral vectors • viscoelastic gel




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P. L. Sinn, E. R. Burnight, M. A. Hickey, G. W. Blissard, and P. B. McCray Jr.
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J. Virol., October 15, 2005; 79(20): 12818 - 12827.
[Abstract] [Full Text] [PDF]




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