Specificity of Short Interfering RNA Determined through Gene Expression Signatures

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 tar...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-05, Vol.100 (11), p.6347-6352
Main Authors: Semizarov, Dimitri, Frost, Leigh, Sarthy, Aparna, Kroeger, Paul, Halbert, Donald N., Fesik, Stephen W.
Format: Article
Language:English
Subjects:
Arrays
Biological Sciences
Density
DNA
Down regulation
Gene Expression
Gene expression regulation
Genes
Messenger RNA
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Small Interfering - metabolism
Signatures
Small interfering RNA
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1131959100