Recently, efforts have been dedicated to generate defined lineages of neural cells from ESCs and iPSCs. These cells serve to better understand the molecular mechanisms underlying the pathophysiology of many intractable neurodegenerative diseases such as PD, HD, ALS, and AD aiming for the development of effective therapies. The present lack of precise models of these diseases conveys the significant discrepancies in understanding the mechanisms underlying their pathophysiology. In the last decade, the ability to reprogram somatic cells into iPSCs have enhanced the effectiveness of human in vitro models of neurological diseases (Mungenast et al., 2016). Moreover, the differentiation of these iPSCs into disease-relevant cell types have allowed comprehensive molecular analyses of multiple disease states. Indeed, neurons differentiated from patient-specific iPSCs provide a valuable tool to model specific molecular phenotypes of neurodegenerative diseases in vitro (Heman-Ackah et al., 2016). In this aspect, the introduction of human iPSCs with disease-specific genetic backgrounds requires precise and flexible genome engineering tools.
