title: A novel chimeric adenoassociated virus 2/human bocavirus 1 parvovirus vector efficiently transduces human airway epithelia.
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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Yan
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Keiser
authors.forename: Yi
authors.initials: Y
authors.lastname: Song
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Deng
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
authors.forename: John F
authors.initials: JF
authors.lastname: Engelhardt
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D002678:Chimera; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral; D057809:HEK293 Cells; D056661:Human bocavirus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic; D056189:Viral Tropism
chemical_list: D036022:Capsid Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
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