RNAi screening for the discovery of novel modulators of human disease.

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.