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The ability to modulate gene expression with reverse genetics methods is of great importance for both basic and translational research. Gene silencing allows identifying players involved in cellular processes such as signaling, metabolism, and differentiation, among others. The discovery of RNA interference (RNAi) 20 years ago suddenly allowed the downregulation of genes in mammalian cultured cells. Since then, other gene silencing methods based on genome editing have been developed such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and, more recently, the clustered regularly interspaced short palindromic repeats/Cas (CRISPR/Cas) systems. Thus, many forward genetic methods now exist to downregulate gene expression in mammalian cells, each having its advantages and drawbacks.

The King Is Dead, Long Live the King! JBS Special Issue on Screening by RNAi and Precise Genome Editing Technologies