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Abstract
Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassaemia or sicklecell 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 (Duffynull), GPB (Ss 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.
Original language | English |
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Article number | e8454 |
Number of pages | 11 |
Journal | EMBO Molecular Medicine |
Volume | 10 |
Issue number | 5 |
Early online date | 26 Apr 2018 |
DOIs | |
Publication status | E-pub ahead of print - 26 Apr 2018 |
Structured keywords
- BrisSynBio
- Bristol BioDesign Institute
Keywords
- Synthetic Biology
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Projects
- 1 Active
Datasets
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WGS data from EMM-2017-08454
Toye, A. M. (Creator) & Satchwell, T. J. (Creator), University of Bristol, 26 Apr 2018
DOI: 10.5523/bris.3owu3wwvhghy5278tzd6b8wutz, http://data.bris.ac.uk/data/dataset/3owu3wwvhghy5278tzd6b8wutz
Dataset
Equipment
Profiles
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Professor Jan Frayne
- School of Biochemistry - Professor in Molecular Cell Biology
- Fundamental Bioscience
Person: Academic , Member
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Professor Ash M Toye
- School of Biochemistry - Professor of Cell Biology
- Fundamental Bioscience
- Dynamic Cell Biology
Person: Academic , Member