TY - JOUR T1 - <em>In Vivo</em> Delivery of Therapeutic Molecules by Transplantation of Genome-Edited Induced Pluripotent Stem Cells JF - bioRxiv DO - 10.1101/2023.01.03.522057 SP - 2023.01.03.522057 AU - Ittetsu Nakajima AU - Takahiro Tsukimura AU - Terumi Ono AU - Tomoko Shiga AU - Hiroshi Shitara AU - Tadayasu Togawa AU - Hitoshi Sakuraba AU - Yuichiro Miyaoka Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/01/03/2023.01.03.522057.abstract N2 - Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of α-Galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified α-N-acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules.Competing Interest StatementThe authors have declared no competing interest. ER -