Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing

Hawksworth, Joseph; Satchwell, Timothy J.; Meinders, Marjolein; Daniels, Deborah E.; Regan, Fiona; Thornton, Nicole M.; Wilson, Marieangela C.; Dobbe, Johannes G.G.; Streekstra, Geert J.; Trakarnsanga, Kongtana; Heesom, Kate J.; Anstee, David J.; Frayne, Jan; Toye, Ashley M.

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 (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.

• Journal Article Type: Article
• Acceptance Date: Mar 26, 2018
• Online Publication Date: Apr 26, 2018
• Publication Date: Jun 1, 2018
• Deposit Date: Jul 11, 2024
• Publicly Available Date: Jul 12, 2024
• Journal: EMBO Molecular Medicine
• Print ISSN: 1757-4676
• Electronic ISSN: 1757-4684
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 6
• Article Number: e8454
• DOI: https://doi.org/10.15252/emmm.201708454
• Public URL: https://uwe-repository.worktribe.com/output/12121460