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Title: Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing
Authors: Joseph Hawksworth
Timothy J. Satchwell
Marjolein Meinders
Deborah E. Daniels
Fiona Regan
Nicole M. Thornton
Marieangela C. Wilson
Johannes G.G. Dobbe
Geert J. Streekstra
Kongtana Trakarnsanga
Kate J. Heesom
David J. Anstee
Jan Frayne
Ashley M. Toye
Imperial College Healthcare NHS Trust
NHS Blood and Transplant
University of Bristol
Faculty of Medicine, Siriraj Hospital, Mahidol University
Amsterdam UMC - University of Amsterdam
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jun-2018
Citation: EMBO Molecular Medicine. Vol.10, No.6 (2018)
Abstract: © 2018 The Authors. Published under the terms of the CC BY 4.0 license Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassaemia or sickle-cell disease. With repeated transfusion, alloimmunisation often occurs due to incompatibility at the level of minor blood group antigens. We use CRISPR-mediated genome editing of an immortalised human erythroblast cell line (BEL-A) to generate multiple enucleation competent cell lines deficient in individual blood groups. Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rh null ), Kell (K 0 ), Duffy (Fy null ), GPB (S−s−U−). These cells can be differentiated to generate deformable reticulocytes, illustrating the capacity for coexistence of multiple rare blood group antigen null phenotypes. This study provides the first proof-of-principle demonstration of combinatorial CRISPR-mediated blood group gene editing to generate customisable or multi-compatible RBCs for diagnostic reagents or recipients with complicated matching requirements.
ISSN: 17574684
Appears in Collections:Scopus 2018

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