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

2009年4月至2012年3月，为了开发家族性淀粉样变性多神经病变（FAP）的根治性治疗方法，我们从FAP患者或具有人类ATTR V30M基因的转基因大鼠（ATTR V30M Tg大鼠）中获得体细胞，并将其重编程为多能性，生成FAP特异性诱导多能干细胞（iPS），并评估了FAP特异性iPS细胞与单链寡核苷酸（SSOs）基因修复治疗相结合的肝细胞替代治疗的可能性。在接下来的项目中，我们将重点利用这些FAP特异性的iPS细胞，利用现有的有用的FAP动物模型ATTR V30M Tg大鼠进行体内实验，阐明FAP的确切发病机制，提高基因转换率的效率，并确定肝细胞替代治疗的可行性。

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.