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dc.contributor.authorKhairuddin, Norliana
dc.contributor.authorBlake, Stephen J.
dc.contributor.authorFirdaus, Farah
dc.contributor.authorSteptoe, Raymond J.
dc.contributor.authorBehlke, Mark A.
dc.contributor.authorHertzog, Paul J.
dc.contributor.authorMcMillan, Nigel
dc.date.accessioned2018-11-16T01:48:50Z
dc.date.available2018-11-16T01:48:50Z
dc.date.issued2014
dc.identifier.issn08189641en_US
dc.identifier.doi10.1038/icb.2013.75en_US
dc.identifier.urihttp://hdl.handle.net/10072/138134
dc.description.abstractSmall interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-a (IFNa) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNa were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofpagefrom156en_US
dc.relation.ispartofpageto163en_US
dc.relation.ispartofissue2en_US
dc.relation.ispartofjournalImmunology and Cell Biologyen_US
dc.relation.ispartofvolume92en_US
dc.subject.fieldofresearchCancer Therapy (excl. Chemotherapy and Radiation Therapy)en_US
dc.subject.fieldofresearchcode111204en_US
dc.titleIn vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumoursen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dc.description.versionPost-printen_US
gro.rights.copyright© 2013 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.en_US
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