Efficient CRISPR/Cas9-based gene correction in induced pluripotent stem cells established from fibroblasts of patients with sickle cell disease

Since Takahashi and Yamanaka (1) first reported the successful establishment of induced pluripotent stem cells (iPSCs), these cells have been an important resource for regenerative medicine and gene therapy strategies (2). In particular, the use of iPSCs helps avoid the ethical concerns associated with the use of human embryonic stem cells (ESCs) established from donor oocytes, and mitigate the possibility of immune rejection by allowing the generation of “patient-specific” pluripotent stem cells from somatic cell types (3). Furthermore, the recent advent of site-specific genome-editing technologies, such as the CRISPR/Cas9 system, has enabled “gene correction” by inserting normal sequences or deleting mutated sequences from mutated sites in the genome (4,5). These techniques have opened the doors to curing genetic disorders caused by mutations in a specific gene. One promising approach is gene correction in iPSCs established from somatic cells of patients with genetic defects. The differentiated derivatives (e.g., neurons, hematopoietic cells, and cardiomyocytes) of successfully genome-edited iPSCs can be used for the replacement of damaged tissues through autologous transplantation. In fact, successful gene correction has been reported in iPSCs derived from patients with cystic fibrosis and
β-thalassemia (6-10).