Journal article
Distinct Transduction Difference Between Adeno-Associated Virus Type 1 and Type 6 Vectors in Human Polarized Airway Epithelia
Gene therapy, Vol.20(3), pp.328-337
03/2013
DOI: 10.1038/gt.2012.46
PMCID: PMC3443503
PMID: 22695783
Abstract
Of the many biologically isolated AAV serotypes, AAV1 and AAV6 share the highest degree of sequence homology, with only six different capsid residues. We compared the transduction efficiencies of rAAV1 and rAAV6 in primary polarized human airway epithelia (HAE) and found significant differences in their abilities to transduce epithelia from the apical and basolateral membranes. rAAV1 transduction was ~10-fold higher than rAAV6 following apical infection, while rAAV6 transduction was ~10-fold higher than rAAV1 following basolateral infection. Furthermore, rAAV6 demonstrated significant polarity of transduction (100-fold; basolateral≫apical), while rAAV1 transduced from both membranes with equal efficiency. To evaluate capsid residues responsible for the observed serotype differences, we mutated the six divergent amino acids either alone or in combination. Results from these studies demonstrated that capsid residues 418 and 513 most significantly controlled membrane polarity differences in transduction between serotypes, with the rAAV6-D418E/K513E mutant demonstrating decreased (~10-fold) basolateral transduction and the rAAV1-E418D/E513K mutant demonstrating a transduction polarity identical to rAAV6-WT. However, none of the rAAV6 mutants obtained apical transduction efficiencies of rAAV1-WT, suggesting that all six divergent capsid residues in AAV1 act in concert to improve apical transduction of HAE.
Details
- Title: Subtitle
- Distinct Transduction Difference Between Adeno-Associated Virus Type 1 and Type 6 Vectors in Human Polarized Airway Epithelia
- Creators
- Ziying Yan - Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, IA 52242, USADiana Chi Man Lei-Butters - Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, IA 52242, USANicholas W Keiser - Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, IA 52242, USAJohn F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.20(3), pp.328-337
- DOI
- 10.1038/gt.2012.46
- PMID
- 22695783
- PMCID
- PMC3443503
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025367002771
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