Fakhiri, Julia, Schneider, Marc A., Puschhof, Jens, Stanifer, Megan, Schildgen, Verena, Holderbach, Stefan, Voss, Yannik, El Andari, Jihad, Schildgen, Oliver ORCID: 0000-0003-4297-9627, Boulant, Steeve ORCID: 0000-0001-8614-4993, Meister, Michael, Clevers, Hans, Yan, Ziying ORCID: 0000-0001-8210-5567, Qiu, Jianming and Grimm, Dirk (2019). Novel Chimeric Gene Therapy Vectors Based on Adeno-Associated Virus and Four Different Mammalian Bocaviruses. Mol.Ther.-Methods Clin. Dev., 12. S. 202 - 223. CAMBRIDGE: CELL PRESS. ISSN 2329-0501

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Abstract

Parvoviruses are highly attractive templates for the engineering of safe, efficient, and specific gene therapy vectors, as best exemplified by adeno-associated virus (AAV). Another candidate that currently garners increasing attention is human bocavirus 1 (HBoV1). Notably, HBoV1 capsids can cross-package recombinant (r) AAV2 genomes, yielding rAAV2/HBoV1 chimeras that specifically transduce polarized human airway epithelia (pHAEs). Here, we largely expanded the repertoire of rAAV/BoV chimeras, by assembling packaging plasmids encoding the capsid genes of four additional primate bocaviruses, HBoV2-4 and GBoV (Gorilla BoV). Capsid protein expression and efficient rAAV cross-packaging were validated by immunoblotting and qPCR, respectively. Interestingly, not only HBoV1 but also HBoV4 and GBoV transduced pHAEs as well as primary human lung organoids. Flow cytometry analysis of pHAEs revealed distinct cellular specificities between the BoV isolates, with HBoV1 targeting ciliated, club, and KRT5+ basal cells, whereas HBoV4 showed a preference for KRT5+ basal cells. Surprisingly, primary human hepatocytes, skeletal muscle cells, and T cells were also highly amenable to rAAV/BoV transduction. Finally, we adapted our pipeline for AAV capsid gene shuffling to all five BoV isolates. Collectively, our chimeric rAAV/BoV vectors and bocaviral capsid library represent valuable new resources to dissect BoV biology and to breed unique gene therapy vectors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fakhiri, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, Marc A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puschhof, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stanifer, MeganUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schildgen, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holderbach, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voss, YannikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El Andari, JihadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schildgen, OliverUNSPECIFIEDorcid.org/0000-0003-4297-9627UNSPECIFIED
Boulant, SteeveUNSPECIFIEDorcid.org/0000-0001-8614-4993UNSPECIFIED
Meister, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clevers, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yan, ZiyingUNSPECIFIEDorcid.org/0000-0001-8210-5567UNSPECIFIED
Qiu, JianmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimm, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-153735
DOI: 10.1016/j.omtm.2019.01.003
Journal or Publication Title: Mol.Ther.-Methods Clin. Dev.
Volume: 12
Page Range: S. 202 - 223
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2329-0501
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HIGH-EFFICIENCY TRANSDUCTION; HUMAN PARVOVIRUS B19; PACKAGING CAPACITY; IN-VITRO; IMMUNE-RESPONSES; VIRAL VECTORS; AAV2 VECTORS; 1 INFECTION; HUMAN-CELLS; EXPRESSIONMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15373

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