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Article: Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

TitleInhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules
Authors
KeywordsAdeno-associated viral vector
Antiviral therapy
Hepatitis B virus
Hydrodynamic transfection
RNA interference
Issue Date2009
PublisherKorean Society for Biochemistry and Molecular Biology. The Journal's web site is located at http://www.jbmb.or.kr/index.html
Citation
Bmb Reports, 2009, v. 42 n. 1, p. 59-64 How to Cite?
AbstractHepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by 87±4, 80.3±2.6 and 86.2±7% respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.
Persistent Identifierhttp://hdl.handle.net/10722/58367
ISSN
2015 Impact Factor: 2.782
2015 SCImago Journal Rankings: 1.203
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Zen_HK
dc.contributor.authorHe, Mlen_HK
dc.contributor.authorYao, Hen_HK
dc.contributor.authorDong, Qmen_HK
dc.contributor.authorChen, Ycen_HK
dc.contributor.authorChan, Cyen_HK
dc.contributor.authorZheng, Bjen_HK
dc.contributor.authorYuen, Kyen_HK
dc.contributor.authorPeng, Yen_HK
dc.contributor.authorSun, Qen_HK
dc.contributor.authorYang, Xen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorKung, Hfen_HK
dc.date.accessioned2010-05-31T03:29:04Z-
dc.date.available2010-05-31T03:29:04Z-
dc.date.issued2009en_HK
dc.identifier.citationBmb Reports, 2009, v. 42 n. 1, p. 59-64en_HK
dc.identifier.issn1976-6696en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58367-
dc.description.abstractHepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by 87±4, 80.3±2.6 and 86.2±7% respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.en_HK
dc.languageengen_HK
dc.publisherKorean Society for Biochemistry and Molecular Biology. The Journal's web site is located at http://www.jbmb.or.kr/index.htmlen_HK
dc.relation.ispartofBMB Reportsen_HK
dc.subjectAdeno-associated viral vectoren_HK
dc.subjectAntiviral therapyen_HK
dc.subjectHepatitis B virusen_HK
dc.subjectHydrodynamic transfectionen_HK
dc.subjectRNA interferenceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshDNA, Viral - geneticsen_HK
dc.subject.meshDependovirus - geneticsen_HK
dc.subject.meshGene Expression Regulation, Viral - drug effectsen_HK
dc.subject.meshGenetic Vectors - geneticsen_HK
dc.subject.meshHepatitis B Surface Antigens - blood - geneticsen_HK
dc.subject.meshHepatitis B e Antigens - blood - geneticsen_HK
dc.subject.meshHepatitis B virus - drug effects - genetics - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLiver - pathology - virologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshPlasmids - geneticsen_HK
dc.subject.meshRNA, Small Interfering - genetics - pharmacologyen_HK
dc.subject.meshVirus Replication - drug effectsen_HK
dc.titleInhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA moleculesen_HK
dc.typeArticleen_HK
dc.identifier.emailZheng, Bj:bzheng@hkucc.hku.hken_HK
dc.identifier.emailYuen, Ky:kyyuen@hkucc.hku.hken_HK
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityZheng, Bj=rp00353en_HK
dc.identifier.authorityYuen, Ky=rp00366en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid19192395-
dc.identifier.scopuseid_2-s2.0-62349120881en_HK
dc.identifier.hkuros154394en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-62349120881&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume42en_HK
dc.identifier.issue1en_HK
dc.identifier.spage59en_HK
dc.identifier.epage64en_HK
dc.identifier.isiWOS:000263337500010-
dc.publisher.placeKorea, Republic ofen_HK
dc.identifier.scopusauthoridLi, Z=36064156900en_HK
dc.identifier.scopusauthoridHe, Ml=35080389700en_HK
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridDong, Qm=8437495200en_HK
dc.identifier.scopusauthoridChen, Yc=24075600300en_HK
dc.identifier.scopusauthoridChan, Cy=22033276600en_HK
dc.identifier.scopusauthoridZheng, Bj=7201780588en_HK
dc.identifier.scopusauthoridYuen, Ky=36078079100en_HK
dc.identifier.scopusauthoridPeng, Y=35249237100en_HK
dc.identifier.scopusauthoridSun, Q=35206599000en_HK
dc.identifier.scopusauthoridYang, X=8210555000en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridKung, Hf=7402514190en_HK

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