Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing
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‐mediat...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-04-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201708454 |
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| author | Joseph Hawksworth Timothy J Satchwell Marjolein Meinders Deborah E Daniels Fiona Regan Nicole M Thornton Marieangela C Wilson Johannes GG Dobbe Geert J Streekstra Kongtana Trakarnsanga Kate J Heesom David J Anstee Jan Frayne Ashley M Toye |
| author_facet | Joseph Hawksworth Timothy J Satchwell Marjolein Meinders Deborah E Daniels Fiona Regan Nicole M Thornton Marieangela C Wilson Johannes GG Dobbe Geert J Streekstra Kongtana Trakarnsanga Kate J Heesom David J Anstee Jan Frayne Ashley M Toye |
| author_sort | Joseph Hawksworth |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9af938bdb64040d3b9bf6a27b7e9cbb8 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2018-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-9af938bdb64040d3b9bf6a27b7e9cbb82025-08-20T03:42:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-04-0110611110.15252/emmm.201708454Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editingJoseph Hawksworth0Timothy J Satchwell1Marjolein Meinders2Deborah E Daniels3Fiona Regan4Nicole M Thornton5Marieangela C Wilson6Johannes GG Dobbe7Geert J Streekstra8Kongtana Trakarnsanga9Kate J Heesom10David J Anstee11Jan Frayne12Ashley M Toye13School of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolImperial College Healthcare NHS TrustInternational Blood Group Reference Laboratory, National Health Service (NHS) Blood and TransplantSchool of Biochemistry, University of BristolDepartment of Biomedical Engineering and Physics, Academic Medical Center, University of AmsterdamDepartment of Biomedical Engineering and Physics, Academic Medical Center, University of AmsterdamDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolAbstract 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.https://doi.org/10.15252/emmm.201708454BEL‐ACRISPRerythroidtransfusionuniversal donor |
| spellingShingle | Joseph Hawksworth Timothy J Satchwell Marjolein Meinders Deborah E Daniels Fiona Regan Nicole M Thornton Marieangela C Wilson Johannes GG Dobbe Geert J Streekstra Kongtana Trakarnsanga Kate J Heesom David J Anstee Jan Frayne Ashley M Toye Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing EMBO Molecular Medicine BEL‐A CRISPR erythroid transfusion universal donor |
| title | Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing |
| title_full | Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing |
| title_fullStr | Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing |
| title_full_unstemmed | Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing |
| title_short | Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing |
| title_sort | enhancement of red blood cell transfusion compatibility using crispr mediated erythroblast gene editing |
| topic | BEL‐A CRISPR erythroid transfusion universal donor |
| url | https://doi.org/10.15252/emmm.201708454 |
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