Journal
EMBO MOLECULAR MEDICINE
Volume 10, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201708454
Keywords
BEL-A; CRISPR; erythroid; transfusion; universal donor
Categories
Funding
- NHS Blood and Transplant RD committee [NHSBT WT15-04, WT15-05]
- National Institute for Health (NHIR) [NIHR-BTRU-2015-10032]
- EPSRC/BBSRC SynBio Centre CDT PhD
- Defence Science and Technology Laboratory
- NIHR BTRU
- BrisSynBio via a BBSRC/EPSRC Synthetic Biology Research Centre [BB/L01386X/1]
- BBSRC [BB/L01386X/1] Funding Source: UKRI
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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.
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