@article {SandovalENEURO.0419-19.2020, author = {Alfredo Sandoval, Jr. and Hajira Elahi and Jonathan E Ploski}, title = {Genetically Engineering the Nervous System with CRISPR-Cas}, elocation-id = {ENEURO.0419-19.2020}, year = {2020}, doi = {10.1523/ENEURO.0419-19.2020}, publisher = {Society for Neuroscience}, abstract = {The multitude of neuronal subtypes and extensive interconnectivity of the mammalian brain presents a substantial challenge to those seeking to decipher its functions. While the molecular mechanisms of several neuronal functions remain poorly characterized, advances in Next-Generation Sequencing (NGS) and gene-editing technology have begun to close this gap. The Clustered Regularly Interspaced Palindromic Repeats {\textendash} CRISPR Associated Protein (CRISPR-Cas) system has emerged as a powerful genetic tool capable of manipulating the genome of essentially any organism and cell type, an attribute which has advanced our understanding of complex neurological diseases by enabling the rapid generation of novel, disease-relevant in vitro and transgenic animal models. In this review, we discuss recent developments in the rapidly accelerating field of CRISPR-mediated genome engineering. We begin with an overview of the canonical function of the CRISPR platform, followed by a functional review of its many adaptations, with an emphasis on its applications for genetic interrogation of the normal and diseased nervous system. Additionally, we discuss limitations of the CRISPR editing system and suggest how future modifications to existing platforms may advance our understanding of the brain.}, URL = {https://www.eneuro.org/content/early/2020/02/24/ENEURO.0419-19.2020}, eprint = {https://www.eneuro.org/content/early/2020/02/24/ENEURO.0419-19.2020.full.pdf}, journal = {eNeuro} }