This course will cover the basic principles of genome engineering with emphasis on Cas9/CRISPR technology. It will consist of discussion sessions in which students will present assigned manuscripts followed by a general discussion of the topic directed by the instructor. The course will cover the mechanisms of genome editing using host DNA repair systems, the function of Cas9, and how Cas9 can be harnessed to introduce defined mutations into almost any genome. The use of Cas9 to activate or repress genes, alter chromatin modifications, and the application of these Cas9 systems to conducting genome-scale screens in mammalian cells as well as its use in studying cell fate will be highlighted. Finally, we will study how Cas9 methodologies can be used to introduce disease-associated variants into pluripotent stem cells (e.g. iPSCs) that can be differentiated into disease-relevant cell for use in functional genomic studies.