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RNAi-Based Functional Pharmacogenomics

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Disease Gene Identification

Part of the book series: Methods in Molecular Biology ((MIMB,volume 700))

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.

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Acknowledgments

The authors acknowledge the members of the Pharma­ceutical Genomics Division at the Translational Genomics Research Institute. A special acknowledgement goes to Dr. H. Yin, Dr. Q. Que, D. Chow, Dr. G. Basu, Dr. N. Meurice, and Dr. J. Kiefer for their critical feedback.

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Authors and Affiliations

  1. Pharmaceutical Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA

    Sukru Tuzmen

  2. Translational Genomics Research Institute, Phoenix, AZ, USA

    Pinar Tuzmen, Shilpi Arora, Spyro Mousses & David Azorsa

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  1. Sukru Tuzmen
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  2. Pinar Tuzmen
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  3. Shilpi Arora
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Correspondence to Sukru Tuzmen .

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  1. Research Institute, Diabetes, Cardiovascular, &, Translational Genomics, North 5th St. 445, Phoenix, 85004, Arizona, USA

    Johanna K. DiStefano

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Tuzmen, S., Tuzmen, P., Arora, S., Mousses, S., Azorsa, D. (2011). RNAi-Based Functional Pharmacogenomics. In: DiStefano, J. (eds) Disease Gene Identification. Methods in Molecular Biology, vol 700. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-954-3_18

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  • DOI: https://doi.org/10.1007/978-1-61737-954-3_18

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