Journal article
A novel chimeric adenoassociated virus 2/human bocavirus 1 parvovirus vector efficiently transduces human airway epithelia
Molecular therapy, Vol.21(12), pp.2181-2194
12/2013
DOI: 10.1038/mt.2013.92
PMCID: PMC3863803
PMID: 23896725
Abstract
Human bocavirus virus-1 (HBoV1), a newly discovered autonomous parvovirus with a 5,500 nt genome, efficiently infects human-polarized airway epithelia (HAE) from the apical membrane. We hypothesized that the larger genome and high airway tropism of HBoV1 would be ideal for creating a viral vector for lung gene therapy. To this end, we successfully generated recombinant HBoV1 (rHBoV1) from an open reading frames-disrupted rHBoV1 genome that efficiently transduces HAE from the apical surface. We next evaluated whether HBoV1 capsids could package oversized rAAV2 genomes. These studies created a rAAV2/HBoV1 chimeric virus (5.5 kb genome) capable of apically transducing HAE at 5.6- and 70-fold greater efficiency than rAAV1 or rAAV2 (4.7-kb genomes), respectively. Molecular studies demonstrated that viral uptake from the apical surface was significantly greater for rAAV2/HBoV1 than for rAAV2 or rAAV1, and that polarization of airway epithelial cells was required for HBoV1 capsid-mediated gene transfer. Furthermore, rAAV2/HBoV1-CFTR virus containing the full-length cystic fibrosis transmembrane conductance regulator (CFTR) gene coding sequence and the strong CBA promoter efficiently corrected CFTR-dependent chloride transport in cystic fibrosis (CF) HAE. In summary, using the combined advantages of AAV and HBoV1, we have developed a novel and promising viral vector for CF lung gene therapy and also potentially HBoV1 vaccine development.
Details
- Title: Subtitle
- A novel chimeric adenoassociated virus 2/human bocavirus 1 parvovirus vector efficiently transduces human airway epithelia
- Creators
- Ziying Yan - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USANicholas W KeiserYi SongXuefeng DengFang ChengJianming QiuJohn F Engelhardt
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.21(12), pp.2181-2194
- Publisher
- United States
- DOI
- 10.1038/mt.2013.92
- PMID
- 23896725
- PMCID
- PMC3863803
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Grant note
- R01 HL108902 / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS AI085236 / NIAID NIH HHS R21 AI085236 / NIAID NIH HHS HL108902 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025307902771
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