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Our laboratory develops robust protein engineering methods for constructing artificial "designer" DNA-binding domains. Our efforts focus on Cys2His2 zinc fingers and Xanthomonas Transcription Activator-Like Effector (TALE) repeat domains, two motifs that can be used to create proteins with customized DNA-binding specificities. We are also exploring the applications of engineered zinc finger and TALE repeat domain proteins for biological research and gene therapy.
Engineering "designer" DNA-binding domains with novel specificities
The Joung lab develops robust and high-throughput methods for rapidly engineering synthetic zinc finger and TALE repeat domain proteins with novel, defined DNA-binding specificities. We are also developing approaches to define and further improve the activities and specificities of both zinc finger and TALE domain proteins.
Engineered nucleases for targeted, highly efficient genome editing
Zinc finger nucleases (ZFNs) and TALE nucleases (TALENs), consisting of designer zinc fingers or TALE domains fused to a non-specific endonuclease domain, can be used to introduce targeted DNA alterations with high efficiency at specific genomic loci in a variety of different cell types and organisms ranging from human to Drosophila. These alterations result from repair of nuclease-induced double-stranded DNA breaks by normal cellular repair processes (non-homologous end-joining or homologous recombination). On-going projects in the lab are aimed at developing the ZFN and TALEN genome modification methodologies and using them for applications in biological research and gene therapy.
Altering cellular phenotypes using combinatorial transcription factor libraries
We have recently constructed large combinatorial libraries of zinc finger domains which can be fused to various transcriptional regulatory domains (e.g.--activation or repression domains). We are introducing these libraries into human cells to induce specific desired phenotypes and cellular states. We are exploring similar strategies based on combinatorial libraries of TALE-based DNA-binding domains.