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Journal of Virology, July 1999, p. 6085-6088, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Transduction of Well-Differentiated Airway Epithelium by Recombinant Adeno-Associated Virus Is Limited by Vector Entry

Robert Bals,1 Weidong Xiao,1 Nianli Sang,1 Daniel J. Weiner,1,2 Rupalie L. Meegalla,1 and James M. Wilson1,*

Departments of Medicine and Molecular and Cellular Engineering, Institute for Human Gene Therapy, and The Wistar Institute,1 and Division of Pulmonary Medicine, The Children's Hospital of Philadelphia,2 Philadelphia, Pennsylvania 19104

Received 30 November 1998/Accepted 30 March 1999

The limitations of adeno-associated virus (AAV)-mediated vectors for lung-directed gene transfer were investigated by using differentiated human respiratory epithelium in air-liquid interface cultures. Transduction efficiency was high in undifferentiated cells and was enhanced in well-differentiated cells after basolateral application of the vector or after apical application following disruption of tight junctions or pretreatment of the cultures with glycosidases. These results indicate that transduction of airway epithelia by AAV vectors is limited by entry and reinforce the importance of a physical barrier on the airway surface.

* Corresponding author. Mailing address: 3601 Spruce St., 204 Wistar Institute, Philadelphia, PA 19104-4268. Phone: (215) 898-3000. Fax: (215) 898-6588. E-mail: wilsonjm{at}mail.med.upenn.edu.

Journal of Virology, July 1999, p. 6085-6088, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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