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dc.contributor.authorGu, Wenyi
dc.contributor.authorCochrane, Melanie
dc.contributor.authorLeggatt, Graham R
dc.contributor.authorPayne, Elizabeth
dc.contributor.authorChoyce, Allison
dc.contributor.authorZhou, Fang
dc.contributor.authorTindle, Robert
dc.contributor.authorMcMillan, Nigel AJ
dc.date.accessioned2017-05-03T14:56:50Z
dc.date.available2017-05-03T14:56:50Z
dc.date.issued2009
dc.date.modified2012-05-29T22:39:40Z
dc.identifier.issn0027-8424
dc.identifier.doi10.1073/pnas.0812085106
dc.identifier.urihttp://hdl.handle.net/10072/44398
dc.description.abstractRNA interference (RNAi) for cancer treatment relies on the ability to directly kill cancer cells via down-regulation of target genes, but issues of delivery and efficacy have limited clinical adoption. Furthermore, current studies using immune-deficient animal models disregard potential interactions with the adaptive immune system. It has previously been observed that certain viral antigens appear to be more rapidly presented to the immune system than normal proteins due to the production of defective ribosomal products by the virus. Given that RNAi could potentially result in the generation of truncated mRNAs, we wondered whether a similar mechanism of immune presentation of a target gene was possible. Here we show that RNAi-cleaved mRNAs can be translated into incomplete protein, and if cleavage was downstream of cytotoxic T cell epitopes, resulted in increased presentation of target protein and the generation of a tumor-protective immune response. We show that mice inoculated with tumor cells treated with such short hairpin RNAs (shRNAs) were protected from subsequent challenge with untreated tumors. However, protection was only found if shRNAs were targeted downstream of the dominant cytotoxic T cell (CTL) epitope. Our work suggests that RNAi can alter immunity to targets and shows that not all tumor cells require direct RNAi exposure for treatment to be effective in vivo, pointing the way to a new class of RNAi-based therapy.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent286241 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom8314
dc.relation.ispartofpageto8319
dc.relation.ispartofissue20
dc.relation.ispartofjournalProceedings of the National Academy of Sciences
dc.relation.ispartofvolume106
dc.rights.retentionY
dc.subject.fieldofresearchMedical microbiology not elsewhere classified
dc.subject.fieldofresearchcode320799
dc.titleBoth treated and untreated tumors are eliminated by short hairpin RNA-based induction of target-specific immune responses
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2009 National Academy of Sciences. 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.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorMcMillan, Nigel


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