Cellular Engineering and Disease Modeling with Gene-Editing Nucleases

Abstract

Two rapidly evolving technologies are set to intersect at the crossroads of the future of medicine: the knowledge of how to induce and maintain cellular pluripotency, and the ability to precisely manipulate the genome with engineered nucleases. Together, these two advances have significant potential in the development of the next generation of cell and gene therapies. This review will discuss human and animal models of stem cells and the application of engineered nucleases for precision gene targeting and control. For animal studies and models, nucleases have allowed for greater flexibility and expandability. Previously untargetable regions of the murine genome are now accessible via engineered nucleases. Prior to the availability of gene editing proteins, the entire rat genome was largely refractory to gene targeting and manipulation. The ability to engineer larger animals may reduce the transplant organ gap and increase the yields of food for an expanding population. Lastly, the ability to modify stem cells of hematopoietic, embryonic, or somatic origin will allow for more relevant disease modeling, and more targeted and effective therapies. Collectively, the efficiency of gene editing nucleases and the ability to apply them across cells of multiple species allows for new research opportunities, more flexibility, and greater accuracy in choosing the model best suited for genome manipulation.