Young-Hoon Kim1,2, Hyun O. Kim3, Eun J. Baek4, Ryo Kurita5, Hyuk-Jin Cha6, Yukio Nakamura7 & Hyongbum Kim1,2
1 Graduate School of Biomedical Science and Engineering/College of Medicine, Hanyang University, Seoul 133-791, South Korea. 2 Department of Pharmacology, Brain Korea 21 Plus Project for Medical Sciences, Graduate Program of Nano Science and Technology, Yonsei University College of Medicine, Seoul 120-752, South Korea. 3 Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea. 4 Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul 133-791, South Korea. 5 Department of Research and Development, Central Blood Institute, Japanese Red Cross Society, Tokyo 135-8521, Japan. 6 Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea. 7 Division of Cell Engineering, RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
Correspondence to : Hyongbum Kim
Group O D-negative blood cells are universal donors in transfusion medicine and methods for converting other blood groups into this universal donor group have been researched. However, conversion of D-positive cells into D-negative is yet to be achieved, although conversion of group A or B cells into O cells has been reported. The Rh D blood group is determined by the RHD gene, which encodes a 12-transmembrane domain protein. Here we convert Rh D-positive erythroid progenitor cells into D-negative cells using RHD-targeting transcription activator-like effector nucleases (TALENs). After transfection of TALEN-encoding plasmids, RHD-knockout clones are obtained. Erythroid-lineage cells differentiated from these knockout erythroid progenitor cells do not agglutinate in the presence of anti-D reagents and do not express D antigen, as assessed using flow cytometry. Our programmable nuclease-induced blood group conversion opens new avenues for compatible donor cell generation in transfusion medicine.