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Viruses 2016, 8(5), 129;

Re-Designed Recombinant Hepatitis B Virus Vectors Enable Efficient Delivery of Versatile Cargo Genes to Hepatocytes with Improved Safety

Key Laboratory of Medical Molecular Virology (MOH & MOE) and Institutes of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Joanna Parish
Received: 23 February 2016 / Revised: 22 April 2016 / Accepted: 4 May 2016 / Published: 10 May 2016
(This article belongs to the Section Animal Viruses)
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Hepatitis B virus (HBV) takes humans as its sole natural host, and productive infection in vivo is restricted exclusively to hepatocytes in the liver. Consequently, HBV-derived viral vectors are attractive candidates for liver-targeting gene therapies. Previously, we developed a novel recombinant HBV vector, designated 5c3c, from a highly replicative clinical isolate. 5c3c was demonstrated to be capable of efficiently delivering protein or RNA expression into infected primary tupaia hepatocytes (PTH), but the design of 5c3c imposes stringent restrictions on inserted sequences, which have limited its wider adoption. In this work, we addressed issues with 5c3c by re-designing the insertion strategy. The resultant vector, designated 5dCG, was more replicative than parental 5c3c, imposed no specific restrictions on inserted sequences, and allowed insertion of a variety of cargo genes without significant loss of replication efficiency. 5dCG-based recombinant HBV effectively delivered protein and RNA expression into infected PTH. Furthermore, due to the loss of functional core ORF, 5dCG vectors depend on co-infecting wild type HBV for replication and efficient expression of cargo genes. Development of the improved 5dCG vector makes wider applications of recombinant HBV possible, while dependence on co-infecting wild type HBV results in improved safety for certain in vivo applications. View Full-Text
Keywords: HBV; gene therapy; viral vector; hepatocyte HBV; gene therapy; viral vector; hepatocyte

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Bai, W.; Cui, X.; Chen, R.; Tao, S.; Hong, R.; Zhang, J.; Zhang, J.; Wang, Y.; Xie, Y.; Liu, J. Re-Designed Recombinant Hepatitis B Virus Vectors Enable Efficient Delivery of Versatile Cargo Genes to Hepatocytes with Improved Safety. Viruses 2016, 8, 129.

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