Antitumor effects of retargeted AAV2 virus on ovarian cancer in vivo

Title
Antitumor effects of retargeted AAV2 virus on ovarian cancer in vivo
Authors
안형준이성진
Keywords
AAV virus; retargeting; ovarian cancer; anticancer effect; gene silencing
Issue Date
2020-05
Publisher
The 25th Annual Meeting of the RNA Society
Abstract
Adeno-associatedvirus(AAV)isapromisingvectorforsystemicdeliveryofsiRNAduetoitslong-termexpressionabilitywithoutimmunogenicityandpathogenicity.However,itsbroadhosttropismandlackoftissuespecificityhaslimitedclinicalapplicationssuchascancertherapy.Therefore,redirectingthenaturaltropismofAAVvectorstouniquecellsurfaceantigensisanimportantrequirementforinvivoRNAi-basedcancertherapy.Toexploittheoverexpressionpropertyofepithelialcelladhesionmolecule(EpCAM)inspecificcancertypes,weherecreatedanti-EpCAManitibody-conjugatedAAVserotype2(AAV2)vectorsthroughastreptavidin-biotinbridge.Uponintravenousinjection,anti-EpCAM-conjugatedAAV2vectorsshowedprominenttumor-specificaccumulationinEpCAM-positivetumor-bearingmicewithoutundesirablesequestrationinliver.Inaddition,whenloadedwithtransgenestoexpressshRNAagainstepidermalgrowthfactorreceptor(EGFR),systemicallyinjectedanti-EpCAM-conjugatedAAV2/shEGFRvectorsinducedsignificantdownregulationofEGFRexpressionintumors,andeventuallysuppressedtumorgrowthevenatthelongdosingintervaloftwoweeks.Thisinvivoantitumoreffectrepresentstheincreasedinfectionefficacyoftropism-modifiedAAV2vectorsandprolongedexpressionofEGFRshRNAintumortissues.Thus,thisstudysuggeststhegreatpotentialofanti-EpCAM-conjugatedAAV2/shEGFRvectorsasRNAi-basedcancertherapeutics.
URI
http://pubs.kist.re.kr/handle/201004/72313
ISSN
0065-7158
Appears in Collections:
KIST Publication > Conference Paper
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