Journal article
Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes
Human gene therapy, Vol.28(8), pp.612-625
08/01/2017
DOI: 10.1089/hum.2017.060
PMCID: PMC5567599
PMID: 28490200
Abstract
Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attractive for use in gene therapies to treat lung diseases such as cystic fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been hindered by the fact that humans are the only known host for HBoV1 infection. This study reports that rAAV2/HBoV1 vector is capable of efficiently transducing the lungs of both newborn (3- to 7-day-old) and juvenile (29-day-old) ferrets, predominantly in the distal airways. Analyses of
in vivo
,
ex vivo
, and
in vitro
models of the ferret proximal airway demonstrate that infection of this particular region is less effective than it is in humans. Studies of vector binding and endocytosis in polarized ferret proximal airway epithelial cultures revealed that a lack of effective vector endocytosis is the main cause of inefficient transduction
in vitro
. While transgene expression declined proportionally with growth of the ferrets following infection at 7 days of age, reinfection of ferrets with rAAV2/HBoV1 at 29 days gave rise to approximately 5-fold higher levels of transduction than observed in naive infected 29-day-old animals. The findings presented here lay the foundation for clinical development of HBoV1 capsid-based vectors for lung gene therapy in cystic fibrosis using ferret models.
Details
- Title: Subtitle
- Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes
- Creators
- Ziying Yan - 2Center for Gene Therapy, University of Iowa, Iowa City, IowaZehua Feng - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaXingshen Sun - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaYulong Zhang - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaWei Zou - 3Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KansasZekun Wang - 3Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KansasChandler Jensen-Cody - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaBo Liang - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaSoo-Yeun Park - 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaJianming Qiu - 3Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KansasJohn F Engelhardt - 2Center for Gene Therapy, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.28(8), pp.612-625
- DOI
- 10.1089/hum.2017.060
- PMID
- 28490200
- PMCID
- PMC5567599
- NLM abbreviation
- Hum Gene Ther
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Publisher
- Mary Ann Liebert, Inc
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025305102771
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