Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs Chul-Yong Parka,b,1, Jungeun Kimc,d,1, Jiyeon Kweonc,d,1, Jeong Sang Sone, Jae Souk Leea,f, Jeong-Eun Yooa,f, Sung-Rae Chog, Jong-Hoon Kime, Jin-Soo Kimc,d,2, and Dong-Wook Kima,b,f,2 a Department of Physiology, bSeverance Biomedical Research Institute, fBrain Korea 21 Plus Project for Medical Science, and gDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea; cCenter for Genome Engineering, Institute for Basic Science, Seoul 151-742, South Korea; dDepartment of Chemistry, Seoul National University, Seoul 151-742, South Korea; and eLaboratory of Stem Cell Biology, Division of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 136-713, South Korea

Edited by Philip W. Majerus, Washington University Medical School, St. Louis, MO, and approved May 19, 2014 (received for review December 23, 2013)

genome editing

| CRISPR | Cas9 | ZFN

H

emophilia A is one of the most common genetic bleeding disorders, with an incidence of 1 in 5,000 males worldwide (1). This disorder is caused by various genetic mutations, which include large deletions, insertions, inversions, and point mutations, in the X-linked coagulation factor VIII (F8) gene (Haemophilia A Mutation, Structure, Test and Resource Site; http:// hadb.org.uk); a total of 1,492 different mutations are known to cause hemophilia A. Clinical symptoms vary widely according to the genotypes (2). Hemophilia A can be characterized as severe (