Besides the well-recognized risk of tumorigenesis from undifferentiated and partially differentiated pluripotent cells, lurks the risk of tumorigenesis from mutations inadvertently introduced during the intended correction of known mutations. With the advent nuclease-dependent gene editing and its potential for safely correcting genomic mutations (Hsu et al., 2014; Li et al., 2014), autologous cell transplantation of genetically-corrected phenotypes has become an exciting possibility, as first established in mouse models of sickle cell anemia (Hanna et al., 2007). Yet while the potential of any residual PSCs or their incompletely differentiated progeny for undesired expansion after transplant is already a recognized concern, less attention has been paid to the possibility of off-target mutations in the host genome imparted by Crispr-Cas or TALEN editing. The inherent risk of any off-target mutations that might be imparted by gene editing strategies will require stringent measures, such as validation of whole genome sequence, to ensure the safety of genetically-corrected cells before transplant. This is a rapidly evolving field, for which stable regulatory policies have yet to be developed.
