Genome editing and stem cell engineering for disease modeling

The ability to create accurate disease models of human monogenic and complex genetic disorders is very important for the understanding of disease pathogenesis and the development of new therapeutics. Although proof of principle using adult stem cells for disease modeling has been established, induced pluripotent stem cells (iPSCs) have been demonstrated to have the greatest utility for modeling human diseases. Additionally, the latest advances in programmable nucleases have empowered researchers with genome editing tools, such as CRISPR/Cas9, that substantially improve their ability to make precise changes at a defined genomic locus in a broad array of cell types including stem cells. While the utility of these tools is improving, there are several key factors, including design and delivery that should be taken into account to ensure maximum editing efficiency and specificity. Already, these tools have allowed us to efficiently knock out genes and generate single nucleotide polymorphism (SNP) iPSCs. This ability to modify target genomic loci with high efficiency will facilitate the generation of novel genetically modified stem cells for research and therapeutic applications.