Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing.
Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing.
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DOI：
10.15252/emmm.201708454
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发表时间：
2018-06
影响因子：
11.1
通讯作者：
Toye AM
中科院分区：
文献类型：
--
作者：
Hawksworth J;Satchwell TJ;Meinders M;Daniels DE;Regan F;Thornton NM;Wilson MC;Dobbe JG;Streekstra GJ;Trakarnsanga K;Heesom KJ;Anstee DJ;Frayne J;Toye AM
定期输血是地中海贫血或镰状细胞病等红细胞（RBC）疾病患者护理的基石。重复输血时，由于次要血型抗原水平的不相容性，经常发生同种免疫。我们使用CRISPR介导的永生化人成红细胞细胞系（BEL‐A）的基因组编辑来产生单个血型缺陷的多个去核能力细胞系。将编辑组合以产生缺乏导致最常见输血不相容性的多种抗原的单个细胞系：ABO（孟买表型）、Rh（Rhnull）、Kell（K 0）、Duffy（Fynull）、GPB（S-s-U-）。这些细胞可以分化产生可变形的网织红细胞，说明多种罕见血型抗原无效表型共存的能力。这项研究首次证明了组合CRISPR介导的血型基因编辑的原理，为诊断试剂或具有复杂匹配要求的受体生成可定制或多相容的RBC。
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 (K 0), 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.