Title: Center for Synthetic Regulatory Genomics Abstract The Center for Synthetic Regulatory Genomics (SyRGe) is tasked with development and application of revolutionary technology for making dramatic, coordinated changes to extensive gene loci, which will enable broad investigation of the function of regulatory sequences and foster translational applications to biotechnology, personalized medicine and gene therapy. Specifically, we will increase the scope/productivity of the Center from 3 loci per year to 4 (minimum) or 5 loci per year in years 3, 4, and 5. Additionally the Center will further the development of a new big DNA integration technique called mSwAP-In which his capable of iteratively integrating large DNA segments in stem cells, by determining the length limit of DNA that can be introduced at each step.
The last decade in human genetics has seen an explosion in the number of variants linked to common human traits and diseases, but most of these variants lie in non-coding regulatory DNA. This proposal is for a supplement to increase the output of our center by 33-66% in years 3, 4, and 5, and to develop a new method for introducing very large DNAS into stem cells.
