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Methods Mol Biol. 2011;700:271-90. doi: 10.1007/978-1-61737-954-3_18.

RNAi-based functional pharmacogenomics.

Author information

1
Pharmaceutical Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA. stuzmen@tgen.org

Abstract

Experimental alteration of gene expression is a powerful technique for functional characterization of disease genes. RNA interference (RNAi) is a naturally occurring mechanism of gene regulation, which is triggered by the introduction of double-stranded RNA into a cell. This phenomenon can be synthetically exploited to down-regulate expression of specific genes by transfecting mammalian cells with synthetic short interfering RNAs (siRNAs). These siRNAs can be designed to silence the expression of specific genes bearing a particular target sequence in high-throughput (HT) siRNA experimental systems and may potentially be presented as a therapeutic strategy for inhibiting transcriptional regulation of genes. This can constitute a strategy that can inhibit targets that are not tractable by small molecules such as chemical compounds. Large-scale experiments using low-dose drug exposure combined with siRNA also represent a promising discovery strategy for the purpose of identifying synergistic targets that facilitate synthetic lethal combination phenotypes. In light of such advantageous applications, siRNA technology has become an ideal research tool for studying gene function. In this chapter, we focus on the application of RNAi, with particular focus on HT siRNA phenotype profiling, to support cellular pharmacogenomics.

PMID:
21204040
DOI:
10.1007/978-1-61737-954-3_18
[Indexed for MEDLINE]

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