Journal article
Adeno-Associated Virus Type 5 (AAV5) but Not AAV2 Binds to the Apical Surfaces of Airway Epithelia and Facilitates Gene Transfer
Journal of virology, Vol.74(8), pp.3852-3858
04/2000
DOI: 10.1128/JVI.74.8.3852-3858.2000
PMCID: PMC111893
PMID: 10729159
Abstract
In the genetic disease cystic fibrosis, recombinant adeno-associated virus type 2 (AAV2) is being investigated as a vector to transfer CFTR cDNA to airway epithelia. However, earlier work has shown that the apical surface of human airway epithelia is resistant to infection by AAV2, presumably as a result of a lack of heparan sulfate proteoglycans on the apical surface. This inefficiency can be overcome by increasing the amount of vector or by increasing the incubation time. However, these interventions are not very practical for translation into a therapeutic airway-directed vector. Therefore, we examined the efficiency of other AAV serotypes at infecting human airway epithelia. When applied at low multiplicity of infection to the apical surface of differentiated airway epithelia we found that a recombinant AAV5 bound and mediated gene transfer 50-fold more efficiently than AAV2. Furthermore, in contrast to AAV2, AAV5-mediated gene transfer was not inhibited by soluble heparin. Recombinant AAV5 was also more efficient than AAV2 in transferring β-galactosidase cDNA to murine airway and alveolar epithelia in vivo. These data suggest that AAV5-derived vectors bind and mediate gene transfer to human and murine airway epithelia, and the tropism of AAV5 may be useful to target cells that are not permissive for AAV2.
Details
- Title: Subtitle
- Adeno-Associated Virus Type 5 (AAV5) but Not AAV2 Binds to the Apical Surfaces of Airway Epithelia and Facilitates Gene Transfer
- Creators
- Joseph Zabner - Departments of Internal MedicineMichael Seiler - Departments of Internal MedicineRobert Walters - Departments of Internal MedicineRobert M Kotin - Departments of Internal MedicineWendy Fulgeras - Departments of Internal MedicineBeverly L Davidson - Departments of Internal MedicineJohn A Chiorini - Departments of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.74(8), pp.3852-3858
- DOI
- 10.1128/JVI.74.8.3852-3858.2000
- PMID
- 10729159
- PMCID
- PMC111893
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 04/2000
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094644202771
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