High-Precision Genome Surgery in Human Stem Cells

The great potential of human embryonic and adult stem cells in regenerative medicine, gene therapy, drug discovery, and basic research is widely recognized. Many future applications depend on our ability to manipulate stem cell genomes with exogenous DNA in a safe and controllable way. Foreign DNA which carries, for example, a therapeutically active gene, a key regulatory gene involved in cell differentiation, or encodes for small interfering RNA may be inserted into or excised from stem cell genomes. Here, we review current progress and technical challenges in this field of genetic modification with a focus on controlled gene insertion into and ablation from stem cell genomes mediated by site-specific or homologous DNA recombination.