Zinc Fingers, TAL Effectors, or Cas9-Based DNA Binding Proteins: What’s Best for Targeting Desired Genome Loci?

Abstract

Programmable DNA binding proteins (PDPs) that selectively bind user-defined nucleotide sequences can navigate protein domains to any desired target within the genome. Different functional domains can be fused to PDPs to achieve (1) activation or repression of transcription, (2) nicking or cleavage of DNA, or (3) modification or removal of epigenetic marks at the targeted genome spot. Given their broad applicability, the development of highly specific, easy-to-use PDPs has been a holy grail of biotechnology since the determination of the 3-D structure of zinc fingers (ZFs) bound to DNA in 1991 (Pavletich and Pabo, 1991).