Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect

Guoshun Wang; Vladimir Slepushkin; Joseph Zabner; Shaf Keshavjee; Julie C Johnston; Sybille L Sauter; Doug J Jolly; Thomas W Dubensky; Beverly L Davidson; Paul B McCray

doi:10.1172/JCI8390

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Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect

Journal article

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Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect

Guoshun Wang, Vladimir Slepushkin, Joseph Zabner, Shaf Keshavjee, Julie C Johnston, Sybille L Sauter, Doug J Jolly, Thomas W Dubensky, Beverly L Davidson and Paul B McCray

The Journal of clinical investigation, Vol.104(11), pp.R55-R62

12/01/1999

DOI: 10.1172/JCI8390

PMCID: PMC483477

PMID: 10587528

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Abstract

Several problems limit the application of gene transfer to correct the cystic fibrosis (CF) Cl – transport defect in airway epithelia. These include inefficient transduction with vectors applied to the apical surface, a low rate of division by airway epithelial cells, failure of transgene expression to persist, and immune responses to vectors or vector-encoded proteins. To address these issues, we used a feline immunodeficiency virus–based (FIV-based) vector. FIV vector formulated with a calcium chelator transduced fully differentiated, nondividing human airway epithelia when applied to the apical surface. FIV-based vector encoding the cystic fibrosis transmembrane conductance regulator cDNA corrected the Cl – transport defect in differentiated CF airway epithelia for the life of the culture (>3 months). When this approach was applied in vivo, FIV vector expressing β-galactosidase transduced 1–14% of adult rabbit airway epithelia. Transduced cells were present in the conducting airways, bronchioles, and alveoli. Importantly, gene expression persisted, and cells with progenitor capacity were targeted. FIV-based lentiviral vectors may be useful for the treatment of genetic lung diseases such as CF. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin. Invest. 104 :R55–R62 (1999).

Details

Title: Subtitle: Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect
Creators: Guoshun Wang - Program in Gene Therapy, Department of Pediatrics, and
Vladimir Slepushkin - Program in Gene Therapy, Department of Pediatrics, and
Joseph Zabner - Program in Gene Therapy, Department of Pediatrics, and
Shaf Keshavjee - Program in Gene Therapy, Department of Pediatrics, and
Julie C Johnston - Program in Gene Therapy, Department of Pediatrics, and
Sybille L Sauter - Program in Gene Therapy, Department of Pediatrics, and
Doug J Jolly - Program in Gene Therapy, Department of Pediatrics, and
Thomas W Dubensky - Program in Gene Therapy, Department of Pediatrics, and
Beverly L Davidson - Program in Gene Therapy, Department of Pediatrics, and
Paul B McCray - Program in Gene Therapy, Department of Pediatrics, and
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.104(11), pp.R55-R62
Publisher: American Society for Clinical Investigation
DOI: 10.1172/JCI8390
PMID: 10587528
PMCID: PMC483477
ISSN: 0021-9738
eISSN: 1558-8238
Language: English
Date published: 12/01/1999
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093338702771

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