title: Rh D blood group conversion using transcription activator-like effector nucleases.
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.
authors.affiliation: Graduate School of Biomedical Science and Engineering/College of Medicine, Hanyang University, Seoul 133-791, South Korea.|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.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Hyun O
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul 133-791, South Korea.
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Baek
authors.affiliation: Department of Research and Development, Central Blood Institute, Japanese Red Cross Society, Tokyo 135-8521, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kurita
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: Hyuk-Jin
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Division of Cell Engineering, RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Graduate School of Biomedical Science and Engineering/College of Medicine, Hanyang University, Seoul 133-791, South Korea.|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.
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
mesh_terms: D003851:Deoxyribonucleases / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D005312:Fetal Blood; D055786:Gene Knockout Techniques / Q000379:methods*; D018014:Gene Transfer Techniques; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012204:Rh-Hr Blood-Group System / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D003851:Deoxyribonucleases