Abstract:
:Short interfering RNA (siRNA) is widely used for studying gene function and holds great promise as a tool for validating drug targets and treating disease. A critical assumption in these applications is that the effect of siRNA on cells is specific, i.e., limited to the specific knockdown of the target gene. In this article, we characterize the specificity of siRNA by applying gene expression profiling. Several siRNAs were designed against different regions of the same target gene for three different targets. Their effects on cells were compared by using DNA microarrays to generate gene expression signatures. When the siRNA design and transfection conditions were optimized, the signatures for different siRNAs against the same target were shown to correlate very closely, whereas the signatures for different genes revealed no correlation. These results indicate that siRNA is a highly specific tool for targeted gene knockdown, establishing siRNA-mediated gene silencing as a reliable approach for large-scale screening of gene function and drug target validation.
journal_name
Proc Natl Acad Sci U S Aauthors
Semizarov D,Frost L,Sarthy A,Kroeger P,Halbert DN,Fesik SWdoi
10.1073/pnas.1131959100keywords:
subject
Has Abstractpub_date
2003-05-27 00:00:00pages
6347-52issue
11eissn
0027-8424issn
1091-6490pii
1131959100journal_volume
100pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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