Random integration analysis in gene-edited iPS cell lines derived from Werner syndrome patients

Werner syndrome (WS), adult progeria, is characterized by accelerated-aging associated symptoms from a young age. The causative gene, WRN, is a RecQ DNA helicase and involved in DNA maintenance. The most prevalent mutational site is c.3139-1G>C, which is considered a founder mutation in Japan. We have corrected the gene of WS-iPS cells using CRISPR/Cas9 technology targeting the above mutation. Here, we show the results of random integration analysis in those cells.

沃纳综合征（Werner syndrome, WS）又称成年早老症，其特征为自幼便出现与加速衰老相关的临床症状。其致病基因为WRN，该基因属于RecQ DNA解旋酶，参与DNA维持相关的生物学过程。该疾病最常见的突变位点为c.3139-1G>C，此突变被认为是日本人群中的奠基者突变。本研究采用CRISPR/Cas9基因编辑技术靶向上述突变位点，对沃纳综合征诱导多能干细胞（WS-iPS cells）的致病基因进行了校正。本文展示了该校正后细胞的随机整合分析结果。