Transplantation of genome-edited iPS cells delivers therapeutic molecules in vivo

Induced pluripotent stem (iPS) cells have a great impact on biology and medicine, and they are expected to improve regenerative medicine. Since 2014, when a sheet of retinal pigment epithelial cells derived from iPS cells was transplanted into patients with age-related macular degeneration, clinical trials have been conducted with various cell types derived from iPS cells.

While iPS cells derived from healthy individuals have been used thus far, it is expected that transplantation therapy using iPS cells can be enhanced through genetic modification in the future.

Therefore, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the genetical deficiency of ?-Galactosidase A (GLA). We previously developed an engineered enzyme, modified ?-N-acetylgalactosaminidase (mNAGA), to cure Fabry disease by altering the substrate specificity of NAGA, which is a paralog of GLA, into that of GLA.

In this study, which is published in Cell Transplantation, we tested whether transplantation of iPS cells secreting mNAGA by genome editing could supply the GLA activity in vivo. This study demonstrated the potential of cell therapy using genome-edited iPS cells secreting therapeutic molecules. These genome-edited iPS cells could serve as not only a resource for cell transplantation but also a drug delivery system.

Image source: TMIMS.