Specificity of short interfering RNA determined through gene expression signatures.

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.

authors

Semizarov D,Frost L,Sarthy A,Kroeger P,Halbert DN,Fesik SW

doi

10.1073/pnas.1131959100

keywords:

subject

Has Abstract

pub_date

2003-05-27 00:00:00

pages

6347-52

issue

11

eissn

0027-8424

issn

1091-6490

pii

1131959100

journal_volume

100

pub_type

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