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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

RNAi Screening for the Discovery of Novel Modulators of Human Disease

Author(s): Attila A. Seyhan and Terence E. Ryan

Volume 11, Issue 7, 2010

Page: [735 - 756] Pages: 22

DOI: 10.2174/138920110792927766

Price: $65

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Abstract

The development of RNA interference (RNAi)-mediated gene inhibition has changed the direction and speed of drug target discovery and validation. RNAi technology has already influenced strategies for the pharmacological treatment of many diseases including cancer, viral diseases, bacterial pathogens, inflammation, diseases of central nervous systems (CNS), and others. This technology provides a better understanding of the mechanisms which underlie disease pathogenesis and lead to the identification of novel factors that alter the disease phenotype. With the introduction of RNAi libraries in various formats, systematic loss-of-function screens can now be conducted to interrogate the biological functions of specific genes and pathways or an entire genome in various disease areas. The identification of novel mediators of cellular response to disease pathogenesis or treatment approaches may lead to the identification of novel drug targets, development of combinatorial treatment approaches, or pharmacodynamic and patient selection biomarkers and expand our understanding of disease pathogenesis. Here, we review the use of RNAi in various screening formats, and examine the types of targets pursued for oncology and other disease indications.

Keywords: Biomarker, target discovery, RNA interference, RNAi library screen, small interfering RNA (siRNA), short hairpin RNA (shRNA), synthetic lethal screen, target identification, target validation, large number of compounds, lead optimi-zation, clinical trials, RNAi technology, high-throughput RNAi screens, deubiquitinating enzyme CYLD, NF-kB pathway, heterogeneous ribonucleoprotein hnRNPLL, CD45 pre-mRNA splicing, TRAIL, DOBI, intrinsic mitochondrial cell death pathway, MIRSA, MYC, WNT pathway, RNAi reagents, arrayed screening, high content imaging, Caenorhabditis elegans, Drosophila mela-nogaster, homeodomain pituitary transcrip-tion factor PITX1, RAS, , GTPase activating protein RASAL1, Synthetic lethality screens, synthetic suppressor and enhancer genetic interactions, Chemosensitization screens, miRNA Screening, neurofibril-lary tangles (NFT), eukaryotic translation initiation factor 2 kinase 2, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A, A-kinase anchor protein 13 (AKAP13), neurodegenerative diseases, murine leukemia virus, ATP6V0D1, COX6A1, NXF1, Pseudomonas aeruginosa, Brucella, inositol-requiring enzyme, IRE1a, Chlamydia, Listeria, Mycobacterium for-tuitum


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