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Article: Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus

TitleProphylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus
Authors
Issue Date2004
PublisherInternational Medical Press. The Journal's web site is located at http://www.intmedpress.com/Journals/AVT/journals_avt_home.cfm
Citation
Antiviral Therapy, 2004, v. 9 n. 3, p. 365-374 How to Cite?
AbstractObjectives: To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. Methods: 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. Conclusion: Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.
Persistent Identifierhttp://hdl.handle.net/10722/78938
ISSN
2015 Impact Factor: 2.916
2015 SCImago Journal Rankings: 1.361
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorTang, Oen_HK
dc.contributor.authorCheng, Den_HK
dc.contributor.authorXie, FYen_HK
dc.contributor.authorHe, MLen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorWong, KLen_HK
dc.contributor.authorLader, Een_HK
dc.contributor.authorWoodle, MCen_HK
dc.contributor.authorLu, PYen_HK
dc.contributor.authorLi, Ben_HK
dc.contributor.authorZhong, Nen_HK
dc.date.accessioned2010-09-06T07:48:38Z-
dc.date.available2010-09-06T07:48:38Z-
dc.date.issued2004en_HK
dc.identifier.citationAntiviral Therapy, 2004, v. 9 n. 3, p. 365-374en_HK
dc.identifier.issn1359-6535en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78938-
dc.description.abstractObjectives: To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. Methods: 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. Conclusion: Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.en_HK
dc.languageengen_HK
dc.publisherInternational Medical Press. The Journal's web site is located at http://www.intmedpress.com/Journals/AVT/journals_avt_home.cfmen_HK
dc.relation.ispartofAntiviral Therapyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntiviral Agents - chemical synthesisen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCulture Mediaen_HK
dc.subject.meshCytopathogenic Effect, Viral - physiologyen_HK
dc.subject.meshGene Therapyen_HK
dc.subject.meshGenome, Viralen_HK
dc.subject.meshMacaca mulattaen_HK
dc.subject.meshRNA, Small Interfering - chemical synthesis - geneticsen_HK
dc.subject.meshRNA, Viral - antagonists & inhibitors - biosynthesisen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshSARS Virus - genetics - isolation & purification - physiologyen_HK
dc.subject.meshTime Factorsen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshVirus Replication - geneticsen_HK
dc.titleProphylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1359-6535&volume=9&spage=365&epage=374&date=2004&atitle=Prophylactic+and+therapeutic+effects+of+small+interfering+RNA+targeting+SARS-coronavirusen_HK
dc.identifier.emailZheng, BJ: bzheng@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid15259899-
dc.identifier.scopuseid_2-s2.0-3042736199en_HK
dc.identifier.hkuros87352en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3042736199&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.issue3en_HK
dc.identifier.spage365en_HK
dc.identifier.epage374en_HK
dc.identifier.isiWOS:000231615500007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridTang, O=7006723400en_HK
dc.identifier.scopusauthoridCheng, D=55436209600en_HK
dc.identifier.scopusauthoridXie, FY=7202420808en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridWong, KL=7404758889en_HK
dc.identifier.scopusauthoridLader, E=6701692004en_HK
dc.identifier.scopusauthoridWoodle, MC=7005235996en_HK
dc.identifier.scopusauthoridLu, PY=7402293148en_HK
dc.identifier.scopusauthoridLi, B=17135119600en_HK
dc.identifier.scopusauthoridZhong, N=7102137996en_HK

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