Disease-associated genetic variants are being discovered at an astonishing rate and have outstripped the pace at which they can be modeled and understood. Being able to distinguish causal variants from experimental noise is critical for improving our understanding of complex genetic disorders as well as promoting advancements in personalized medicine. Recent progress in genome editing, namely CRISPR-Cas, has provided us with a suite of technologies enabling the rapid and flexible testing of molecular hypothesis for connecting genotype to phenotype in meaningful model systems. I discuss here applications of CRISPR-Cas9 for modeling genetic disorders through modification of the germline and also through genetic perturbation directly in vivo in somatic cells. Finally, I present recent work on combining in vivo genetic perturbation with CRISPR screening and also discuss the future of the technology towards elucidating causal variants at a pace that can match gene discovery.
Randall Platt studied biomedical engineering and chemistry at the University of Utah in Salt Lake City, Utah. In 2011 he obtained an MPhil from Imperial College London in material science and in 2015 a PhD from MIT in biological engineering. After a postdoctoral fellowship at the Broad Institute of MIT and Harvard jointly between Feng Zhang and Paola Arlotta, Platt was appointed as a tenure-track assistant professor in the department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich in 2016. The Platt group develops and applies molecular tools for applications at the intersection of genome engineering, synthetic biology, and neurobiology.