The discovery of zinc fingers and their applications in gene regulation and genome manipulation.

By A. Klug. Annual Review of Biochemistry, 2010

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Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. (2013, background): “In addition, custom DNA-binding proteins, such as zinc finger or TALE proteins, remain somewhat difficult and expensive to design, develop, and empirically test in the cellular context (Klug, 2010).”
Controlling long range genomic interactions at a native locus by targeted tethering of a looping factor (2012, positive): “ZFs have previously been linked to activation domains to successfully activate gene expression (Klug, 2010).”
CRISPR interference (CRISPRi) for sequence-specific control of gene expression (2013, methodology): “…of the repetitive nature of the TALE and zinc-finger proteins, construct development is time-consuming and expensive, making it difficult to build a comprehensive protein library large enough to perturb and interrogate genome-scale regulation or to simultaneously modulate multiple genes 36 .”