Prior to the discovery of CRISPR/Cas systems, gene activation across multiple loci was an arduous process. When using zinc finger proteins or TALE proteins, proteins had to be re-engineered for each gene, making wide-scale gene activation seem next to impossible. The development of CRISPR/Cas systems, however, greatly improved the simplicity of gene activation: rather than requiring protein engineering for each loci, CRISPR/Cas systems only require changing the programmable guide RNA.
Gene activation by dCas9, also referred to as CRISPRa, was initially published in 2013 (Bikard et al., 2013, Perez-Pinera et al., 2013). In the years that followed, innovative methods greatly improved CRISPRa, expanding its practicality and popularity in research (Tanenbaum et al., 2014, Konermann et al., 2015, Chavez et al., 2015).