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Article: Inhibition of HBV gene expression and replication by stably expressed interferon-α1 via adeno-associated viral vectors

TitleInhibition of HBV gene expression and replication by stably expressed interferon-α1 via adeno-associated viral vectors
Authors
KeywordsAdeno-associated virus
Gene therapy
Hepatitis B virus
Hydrodynamic transfection
Interferon-α1
Issue Date2008
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/1099-498X
Citation
Journal Of Gene Medicine, 2008, v. 10 n. 6, p. 619-627 How to Cite?
AbstractBackground: Interferon-α2 (IFNα2) is routinely used for anti-hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half-life, relatively low local concentration and strong side-effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector-delivered IFNα1 was tested for its anti-HBV effects. Methods: Adeno-associated viral vector (AAV-IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme-linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real-time polymerase chain reaction. Results: AAV-IFNα1 effectively transduced HBV-producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV-producing mice, the concentration of IFNα1 in the liver was eight-fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten-fold from day 1-5, and dropped to an undetectable level on day 9 in the AAV-IFNα1 group. Concurrently, the level of viral DNA decreased over 30-fold for several weeks. Conclusions: A single dose administration of AAV-IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV-IFNα1 might be a potential alternative strategy for anti-HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/67994
ISSN
2015 Impact Factor: 3.246
2015 SCImago Journal Rankings: 1.025
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Zen_HK
dc.contributor.authorYao, Hen_HK
dc.contributor.authorMa, Yen_HK
dc.contributor.authorDong, Qen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorPeng, Yen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorChan, CYen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorSung, JJen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorHe, MLen_HK
dc.date.accessioned2010-09-06T06:00:17Z-
dc.date.available2010-09-06T06:00:17Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Gene Medicine, 2008, v. 10 n. 6, p. 619-627en_HK
dc.identifier.issn1099-498Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/67994-
dc.description.abstractBackground: Interferon-α2 (IFNα2) is routinely used for anti-hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half-life, relatively low local concentration and strong side-effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector-delivered IFNα1 was tested for its anti-HBV effects. Methods: Adeno-associated viral vector (AAV-IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme-linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real-time polymerase chain reaction. Results: AAV-IFNα1 effectively transduced HBV-producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV-producing mice, the concentration of IFNα1 in the liver was eight-fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten-fold from day 1-5, and dropped to an undetectable level on day 9 in the AAV-IFNα1 group. Concurrently, the level of viral DNA decreased over 30-fold for several weeks. Conclusions: A single dose administration of AAV-IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV-IFNα1 might be a potential alternative strategy for anti-HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/1099-498Xen_HK
dc.relation.ispartofJournal of Gene Medicineen_HK
dc.rightsJournal of Gene Medicine. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectAdeno-associated virusen_HK
dc.subjectGene therapyen_HK
dc.subjectHepatitis B virusen_HK
dc.subjectHydrodynamic transfectionen_HK
dc.subjectInterferon-α1en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDependovirusen_HK
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_HK
dc.subject.meshGene Expression Regulation, Viral - immunologyen_HK
dc.subject.meshGenetic Vectors - geneticsen_HK
dc.subject.meshHepatitis B - therapyen_HK
dc.subject.meshHepatitis B Antigens - metabolismen_HK
dc.subject.meshHepatitis B virus - immunology - metabolismen_HK
dc.subject.meshImmunotherapy - methodsen_HK
dc.subject.meshInterferon-alpha - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshVirus Replication - immunologyen_HK
dc.titleInhibition of HBV gene expression and replication by stably expressed interferon-α1 via adeno-associated viral vectorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1099-498X&volume=10&issue=6&spage=619&epage=627&date=2008&atitle=Inhibition+of+HBV+gene+expression+and+replication+by+stably+expressed+interferon-α1+via+adeno-associated+viral+vectorsen_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jgm.1174en_HK
dc.identifier.pmid18383553en_HK
dc.identifier.scopuseid_2-s2.0-46649100904en_HK
dc.identifier.hkuros149055en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-46649100904&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue6en_HK
dc.identifier.spage619en_HK
dc.identifier.epage627en_HK
dc.identifier.isiWOS:000257170400003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, Z=36064156900en_HK
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridMa, Y=35746485500en_HK
dc.identifier.scopusauthoridDong, Q=8437495200en_HK
dc.identifier.scopusauthoridChen, Y=24075600300en_HK
dc.identifier.scopusauthoridPeng, Y=7403419265en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridChan, CY=22033276600en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridSung, JJ=35405352400en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK

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