Development and Applications of CRISPR-Cas for Genome Engineering Matthias Heidenreich Broad Institute of MIT and Harvard Novel genetic tools adapted from the microbial CRISPR-Cas system are accelerating the pace of biological research and enabling targeted genetic interrogation in almost any organism and cell type. CRISPR-Cas genetic perturbation is simple and scalable, and expands our ability to elucidate the functional organization of the genome and connect genotype to phenotype both in vitro and in vivo. Here, I give an overview of the development of the CRISPR-Cas technology and present recent work from our laboratory focusing on genome-scale screening in vitro and disease modeling in vivo, and discuss benefits and challenges of genome editing in biomedical research.