24906146

PMC4343198

DP1 MH100706/MH/NIMH NIH HHS/United States
DP1-MH100706/DP/NCCDPHP CDC HHS/United States
R01 DK097768/DK/NIDDK NIH HHS/United States
R01 NS073124/NS/NINDS NIH HHS/United States
R01-NS 07312401),/NS/NINDS NIH HHS/United States

CDC Public Access

Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of mammalian genome function. Analogous to the search function in modern word processors, Cas9 can be guided to specific locations within complex genomes by a short RNA search string. Using this system, DNA sequences within the endogenous genome and their functional outputs are now easily edited or modulated in virtually any organism of choice. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes. In this Review, we describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions. Derived from a remarkable microbial defense system, Cas9 is driving innovative applications from basic biology to biotechnology and medicine.