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

C. P Rooney; G. M Denning; B. P Davis; D. M Flaherty; J. A Chiorini; J Zabner

doi:10.1128/JVI.76.20.10437-10443.2002

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

Journal article

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

C. P Rooney, G. M Denning, B. P Davis, D. M Flaherty, J. A Chiorini and J Zabner

Journal of virology, Vol.76(20), pp.10437-10443

10/2002

DOI: 10.1128/JVI.76.20.10437-10443.2002

PMCID: PMC136549

PMID: 12239320

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Abstract

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.

Gene Therapy

Details

Title: Subtitle: Bronchoalveolar Fluid Is Not a Major Hindrance to Virus-Mediated Gene Therapy in Cystic Fibrosis
Creators: C. P Rooney - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
G. M Denning - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
B. P Davis - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
D. M Flaherty - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
J. A Chiorini - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
J Zabner - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: Journal of virology, Vol.76(20), pp.10437-10443
DOI: 10.1128/JVI.76.20.10437-10443.2002
PMID: 12239320
PMCID: PMC136549
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 10/2002
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Emergency Medicine; Immunology; Internal Medicine
Record Identifier: 9984094593602771

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