CRISPR-targeted genome editing of human induced pluripotent stem cell-derived hepatocytes for the treatment of Wilson’s disease
Rui Wei, Jiayin Yang, Chi-Wa Cheng, Wai-In Ho, Na Li, Yang Hu, Xueyu Hong, Jian Fu, Bo Yang, Yuqing Liu, Lixiang Jiang, Wing‐Hon Lai, Ka‐Wing Au, Wai-Ling Tsang, Yiu-Lam Tse, Kwong‐Man Ng, Miguel A. Esteban, Hung‐Fat Tse
Abstract
BACKGROUND & AIMS: , which encodes a copper-transporting protein. It is characterized by excessive copper deposition in tissues, predominantly in the liver and brain. We sought to investigate whether gene-corrected patient-specific induced pluripotent stem cell (iPSC)-derived hepatocytes (iHeps) could serve as an autologous cell source for cellular transplantation therapy in WD. METHODS: ; ARG). RESULTS: iHeps into ARG mice via intra-splenic injection significantly attenuated the hepatic manifestations of WD. Liver function improved and liver fibrosis decreased due to reductions in hepatic copper accumulation and consequently copper-induced hepatocyte toxicity. CONCLUSIONS: therapy of WD as well as other inherited liver disorders. LAY SUMMARY: Gene correction restored ATP7B function in hepatocytes derived from induced pluripotent stem cells that originated from a patient with Wilson's disease. These gene-corrected hepatocytes are potential cell sources for autologous cell therapy in patients with Wilson's disease.