DOI: 10.1073/pnas.1131959100. Specificity of short interfering RNA determined through gene expression signatures

Specificity of short interfering RNA determined through gene expression signatures

10.1073/pnas.1131959100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

Semizarov, D., Frost, L., Sarthy, A., Kroeger, P., Halbert, D. N., & Fesik, S. W. (2003). Specificity of short interfering RNA determined through gene expression signatures. Proceedings of the National Academy of Sciences, 100(11), 6347â6352.

Authors 6

Dimitri Semizarov (first)
Leigh Frost (additional)
Aparna Sarthy (additional)
Paul Kroeger (additional)
Donald N. Halbert (additional)
Stephen W. Fesik (additional)

References 35 Referenced 381

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Dates

Type	When
Created	22 years, 3 months ago (May 27, 2003, 1:10 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 9:24 p.m.)
Indexed	2 days, 15 hours ago (Sept. 3, 2025, 6:23 a.m.)
Issued	22 years, 3 months ago (May 13, 2003)
Published	22 years, 3 months ago (May 13, 2003)
Published Online	22 years, 3 months ago (May 13, 2003)
Published Print	22 years, 3 months ago (May 27, 2003)

Funders 0

None

BibTeX

@article{Semizarov_2003, title={Specificity of short interfering RNA determined through gene expression signatures}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1131959100}, DOI={10.1073/pnas.1131959100}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Semizarov, Dimitri and Frost, Leigh and Sarthy, Aparna and Kroeger, Paul and Halbert, Donald N. and Fesik, Stephen W.}, year={2003}, month=may, pages={6347–6352} }

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