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© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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 (Rhnull), Kell (K0), Duffy (Fynull), 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.

Details

Title
Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing
Author
Hawksworth, Joseph 1 ; Satchwell, Timothy J 2 ; Meinders, Marjolein 3 ; Daniels, Deborah E 4 ; Regan, Fiona 5 ; Thornton, Nicole M 6 ; Wilson, Marieangela C 3 ; Dobbe, Johannes GG 7 ; Streekstra, Geert J 7 ; Trakarnsanga, Kongtana 8 ; Heesom, Kate J 3 ; Anstee, David J 2 ; Frayne, Jan 4 ; Toye, Ashley M 2   VIAFID ORCID Logo 

 School of Biochemistry, University of Bristol, Bristol, UK; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol, UK 
 School of Biochemistry, University of Bristol, Bristol, UK; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol, UK 
 School of Biochemistry, University of Bristol, Bristol, UK 
 School of Biochemistry, University of Bristol, Bristol, UK; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK 
 Imperial College Healthcare NHS Trust, London, UK; NHS Blood & Transplant, London, UK 
 International Blood Group Reference Laboratory, National Health Service (NHS) Blood and Transplant, Bristol, UK 
 Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 
 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 
Section
Report
Publication year
2018
Publication date
Jun 2018
Publisher
EMBO Press
ISSN
17574676
e-ISSN
17574684
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2051146242
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.