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dc.date.accessioned2017-08-29T15:46:27Z
dc.date.available2017-08-29T15:46:27Z
dc.date.issued2005
dc.identifier.urihttp://hdl.handle.net/10852/57601
dc.description.abstractRNA interference (RNAi) has become an invaluable tool for functional genomics. A critical use of this tool depends on an understanding of the factors that determine the specificity and activity of the active agent, small interfering RNA (siRNA). Several studies have concluded that tolerance of mutations can be considerable and hence lead to off-target effects. In this study, we have investigated in vivo the toleration of wobble (G:U) mutations in high activity siRNAs against Flap Endonuclease 1 (Fen1) and Aquaporin-4 (Aqp4). Mutations in the central part of the antisense strand caused a pronounced decrease in activity, while mutations in the 5′ and 3′ends were tolerated very well. Furthermore, based on analysis of nine different mutated siRNAs with widely differing intrinsic activities, we conclude that siRNA activity can be significantly enhanced by wobble mutations (relative to mRNA), in the 5′ terminal of the antisense strand. These findings should facilitate design of active siRNAs where the target mRNA offers limited choice of siRNA positions. © The Author 2005. Published by Oxford University Press. All rights reserved
 The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.orgen_US
dc.language.isoenen_US
dc.relation.ispartofMoe, Svein Erik Emblem (2017) Basic mechanisms of RNA interference and the brain water channel Aquaporin-4. Doctoral thesis. http://urn.nb.no/URN:NBN:no-60277
dc.relation.urihttp://urn.nb.no/URN:NBN:no-60277
dc.titleTolerated wobble mutations in siRNAs decrease specificity, but can enhance activity in vivoen_US
dc.typeJournal articleen_US
dc.creator.authorHolen, Torgeir
dc.creator.authorMoe, Svein Erik
dc.creator.authorSørbø, Jan Gunnar
dc.creator.authorMeza, Trine J.
dc.creator.authorOttersen, Ole Petter
dc.creator.authorKlungland, Arne
dc.identifier.jtitleNucleic Acids Research
dc.identifier.volume33
dc.identifier.issue15
dc.identifier.startpage4704
dc.identifier.endpage4710
dc.identifier.doihttps://doi.org/10.1093/nar/gki785
dc.identifier.urnURN:NBN:no-60273
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/57601/1/gki785.pdf
dc.type.versionPublishedVersion


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