The Use and Development of TAL Effector Nucleases

Abstract

In 2009 plant geneticists described a novel DNA binding domain derived from transcription activator-like effectors (TALEs) of the plant pathogen genus Xanthomonas. The DNA recognition domain was distinguished by a modular structure in which each building block binds to a single DNA nucleotide. The breakthrough was the identification of the key residues within each block that define its DNA binding properties and to show that specific alterations of these residues allow for the assembly of tailored DNA binding domains able to target any given sequence. This discovery set the stage for the generation of various designer proteins by fusing tailored TALE-based DNA binding domains, with either endonucleases, transcriptional modulators or chromatin remodeling domains, with the final purpose to modify the genome, the transcriptome or the epigenome. In the last few years, the exploitation of designer enzymes has expanded impressively with applications spanning from basic research to systems biology and human gene therapy.