反义RNA寡核苷酸及其与脂质体的复合物对于乙型肝炎病毒的抑制-论文.pdf

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1、II3I3⋯cs、)l，、)nv．pibb．ac．cnInhibitionofHepatitisBVirusinMicebyCationicLiposome／RNAOlig0nucle0tideComplex术ZANYan-Lu一．TIANPo)”(CenterforMolecularVirology,CASKeyLaboratoryofPathogenicMicrobiologyandImmunologyInstituteofMicrobiology,ChineseAcademyofSciences，Beijing100101，Ch

2、ina；UniversityofChineseAcademyofSciences，Beijing100101，China)AbstractWeinvestigatedtheinhibitoryeffectofmodifiedantisenseRNAoligonucleotidesandcationicliposome．RNAcomplexesontherepressionofhepatitisBvirus(耶V)replicationandexpression．ELISAandquantitativeReal—timePCRanaly

3、sisshowedthatHBVreplicationandantigensexpressionbothinpHBV1．3transducedHepG2andHe0G2．2．15cellswerereducedaftertreatmentwithantisenseRNAoligonucleotidesP-2987，X一60andX．519．Subsequently．theantisenseRNAoligonucleotidesandcontrolRNAoligonucleotideswereinjectedviathetailvein

4、intoHBVtransgenicmiceorhydrodynamicallyinjectedmice．IntheHBVtransgenicmice，withthetreatmentofX·519，HBVpregenomicRNAintheliverdecreasedby81％．Cationic1iposomefi,Lrtherincreasedtheinhibitionefectoryto91％．ButnosignificantdiferenceswereobservedforHBVantigensandHBVDNAcopynumb

5、erinthesera．InacuteHBViIlfectionmousemodelbyhydrodynamicinjection．ELISAandquantitativerea1．timePCRanalysisshowedthatX．519significantlyrepressedHBVreplication，asmeasuredbyHBVpregenomicRNA，antigensexpression，andpresenceofHBVDNAinthesera．Takentogether，thesynthesizedantisen

6、seRNAoligonucleotideX一519repressed皿Vreplicationandantigensexpressioninvitroandiniv0．KeywordshepatitisBvires，antisenseRNAoligonucleotides，HBVtransgenicmice，hydrodynamicinjection，cationicliposome—RNAcomplexDoI：10．3724／SP．J．1206．2013．00184HepatitisBvirus(HBV)istheprototypi

7、ca1RNAservesasanmRNAbothfortheviralcorememberoftheHepadnaviridae(hepatotropicDNAproteinandfortheviralpolymerase．virus)family．HBVvirionsaredouble—shelledHBVinfection．whichcancauseacuteorchronicparticles，withanouterlipoproteinenvelopethathepatitis，cirrhosis，andhepatocellu

8、larcarcinoma．isacontainsthreerelatedenvelopeglycoproteins．Thecommonhealthburdenaroundtheworld，especiallyinHBVg