Engineered nucleases for targeted, highly efficient genome manipulation
We have developed highly robust platforms for engineering zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided nucleases (RGNs). Using these three platforms, we have introduced targeted DNA alterations with high efficiency at specific genomic loci in zebrafish, plants, or human somatic and pluripotent stem cells. These alterations result from repair of nuclease-induced double-stranded DNA breaks by normal cellular repair processes (non-homologous end-joining or homologous recombination). Ongoing projects in the lab are aimed at improving these genome modification methodologies and optimizing the technologies for eventual therapeutic applications.
Engineered transcription factors for regulating endogenous gene expression
We have recently demonstrated that both engineered zinc finger or transcription activator-like effector proteins can be used to create artificial customizable transcription factors that can robustly alter expression of endogenous human genes. We are exploring the use of these proteins in both a directed fashion as well as with combinatorial libraries to induce specific desired phenotypes and cellular states in human cells.