Rh D blood group conversion using transcription activator-like effector nucleases

Young-Hoon Kim, Hyun O. Kim, Eun J. Baek, Ryo Kurita, Hyuk-Jin Cha, Yukio Nakamura and Hyongbum Kim ()
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Young-Hoon Kim: Graduate School of Biomedical Science and Engineering/College of Medicine, Hanyang University
Hyun O. Kim: Yonsei University College of Medicine
Eun J. Baek: Hanyang University College of Medicine
Ryo Kurita: Central Blood Institute, Japanese Red Cross Society
Hyuk-Jin Cha: College of Natural Sciences, Sogang University
Yukio Nakamura: RIKEN BioResource Center
Hyongbum Kim: Graduate School of Biomedical Science and Engineering/College of Medicine, Hanyang University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8451

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