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Journal of Virology, October 2002, p. 10437-10443, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10437-10443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bronchoalveolar Fluid Is Not a Major Hindrance to Virus-Mediated Gene Therapy in Cystic Fibrosis

C. P. Rooney,1 G. M. Denning,1 B. P. Davis,1 D. M. Flaherty,1 J. A. Chiorini,2 and J. Zabner1*

Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242,1 Gene Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 208922

Received 18 March 2002/ Accepted 15 June 2002

Successfully targeting the airway epithelium is essential for gene therapy of some pulmonary diseases. However, the airway epithelium is resistant to virus-mediated gene transfer with commonly used vectors. Vectors that interact with endogenously expressed receptors on the apical surface significantly increase gene transfer efficiency. However, other endogenous components involved in host immunity may hinder virus-mediated gene transfer. We tested the effect of bronchoalveolar lavage liquid (BAL) from patients with cystic fibrosis (CF), BAL from subjects without CF (non-CF BAL), Pseudomonas aeruginosa-derived proteins, and an array of inflammatory proteins on gene transfer mediated by adeno-associated virus type 5 (AAV5) and adenovirus targeted to an apically expressed glycosylphosphatidylinositol-modified coxsackie-adenovirus receptor. We found that neither CF BAL nor its components had a significant effect on gene transfer to human airway epithelium by these vectors. Non-CF BAL significantly impaired adenovirus-mediated gene transfer. Removal of immunoglobulins in non-CF BAL restored gene transfer efficiency. As virus vectors are improved and mechanisms of humoral immunity are elucidated, barriers to successful gene therapy found in the complex environment of the human lung can be circumvented.

* Corresponding author. Mailing address: University of Iowa College of Medicine, 540 EMRB, Iowa City, IA 52242. Phone: (319) 335- 7608. Fax: (319) 335-7623. E-mail: joseph-zabner{at}uiowa.edu.

Journal of Virology, October 2002, p. 10437-10443, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10437-10443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.





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