Hepatocyte replacement therapy for familial amybidotic polyneuropathy combining iPS cells and gene-repair therapy

从2009年4月至2012年3月，为了开发家族性淀粉样多发性神经病（FAP）的治愈性治疗，我们从FAP患者或具有人ATTR V30 M基因的转基因大鼠获得体细胞（ATTR V30M Tg大鼠）并重编程为多能性以产生FAP特异性诱导的多能干（iPS）细胞，并评估了结合FAP特异性iPS细胞和使用单链寡核苷酸（SSO）的基因修复疗法的肝细胞替代疗法的可能性。在下一个项目中，我们将专注于使用这些FAP特异性iPS细胞来阐明FAP的确切发病机制，提高基因转化率的效率，并在使用ATTR V30 M Tg大鼠的体内实验中确定肝细胞替代疗法的可用性，ATTR V30 M Tg大鼠是一种现有的有用的FAP动物模型。

From April, 2009 to March, 2012, to develop a curative treatment for familial amyloidotic polyneuropathy(FAP), we obtained somatic cells from FAP patients or transgenic rats possessing a human ATTR V30M gene(ATTR V30M Tg rats) and reprogrammed to pluripotency to generate FAP-specific induced pluripotent stem(iPS) cells, and evaluated the possibility of hepatocyte replacement therapy combining FAP-specific iPS cells and gene-repair therapy using single stranded oligonucleotides(SSOs). In the next project, we will focus on using these FAP-specific iPS cells to elucidate the precise pathogenesis of FAP, improve the efficiency of gene conversion rate, and determine the availability of hepatocyte replacement therapy in the in vivo experiments using ATTR V30M Tg rats, an existing useful FAP animal model.