Gene regulation and genomic engineering using designer TAL effectors

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Frank Notka, Axel Trefzer, Kathrin Brunner, Matthias Arensktter, Matthias Arnold, Jon Chesnut

Lifetechnologies - Geneart, Germany

Transcription activator-like (TAL) effector proteins are naturally occurring transcriptional activators secreted by Xanthomonas spp. into their plant hosts. They are injected into plant host cells and travel to the nucleus where they bind to and activate specific promoter sequences, leading to changes that are permissive for bacterial infection. The deciphering of the TAL effector ‘code’ (repeat variable di-residues) recently led to the engineering of designer TAL effector proteins that could act as a vehicle to locate various functionalities to essentially any open region of the chromosomes of plants, bacteria, yeast, flies and mammalian cells. These tools will have applications from efficient genomic editing and gene knock-out to modulation of specific promoter activities in various species of cells. Here we present an industrial production platform for the synthesis of tailored DNA binding molecules that will allow researchers to choose the functionality they want and deliver it where they want. Designer TAL effector constructs coding for a TAL nuclease or activator are designed to bind a specific 18 or 24 base DNA sequence of choice. Gene activation and gene knock-out examples in mammalian cells illustrate the vast capability of this new genomic tool set.