3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-03

AUTHORS

Amanda Birmingham, Emily M Anderson, Angela Reynolds, Diane Ilsley-Tyree, Devin Leake, Yuriy Fedorov, Scott Baskerville, Elena Maksimova, Kathryn Robinson, Jon Karpilow, William S Marshall, Anastasia Khvorova

ABSTRACT

Off-target gene silencing can present a notable challenge in the interpretation of data from large-scale RNA interference (RNAi) screens. We performed a detailed analysis of off-targeted genes identified by expression profiling of human cells transfected with small interfering RNA (siRNA). Contrary to common assumption, analysis of the subsequent off-target gene database showed that overall identity makes little or no contribution to determining whether the expression of a particular gene will be affected by a given siRNA, except for near-perfect matches. Instead, off-targeting is associated with the presence of one or more perfect 3' untranslated region (UTR) matches with the hexamer or heptamer seed region (positions 2-7 or 2-8) of the antisense strand of the siRNA. These findings have strong implications for future siRNA design and the application of RNAi in high-throughput screening and therapeutic development. More... »

PAGES

199-204

Journal

TITLE

Nature Methods

ISSUE

3

VOLUME

3

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nmeth854

    DOI

    http://dx.doi.org/10.1038/nmeth854

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009898184

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/16489337


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