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A population of autologous cluster of differentiation 34 (CD34)-positive human hematopoietic stem and progenitor cells (hHSPCs) that are ex-vivo gene-edited with the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex at the erythroid lineage-specific enhancer of the B-cell lymphoma/leukemia 11A (BCL11A) gene, with potential usage for transplantation in patients with sickle cell disease (SCD) and beta-thalassemia. CD34-positive HSPCs are isolated from human blood upon apheresis and are genetically modified in vitro using CRISPR/Cas9 technology to specifically disrupt the erythroid enhancer of the BCL11A gene. As BCL11A is a suppressor of fetal hemoglobin (HbF; hemoglobin F) expression, disruption of the BCL11A enhancer decreases the expression of BCL11A and stimulates the expression of HbF in erythrocytes that differentiate from CTX001. Upon infusion back into the patient following myeloablative, conditioning chemotherapy, autologous CRISPR-Cas9 modified/BCL11A enhancer-disrupted CD34+ hHSPCs CTX001 can populate the bone marrow and differentiate into a variety of blood cell types including lymphoid cells, myeloid cells and erythroblasts. The increased production of high levels of HbF in red blood cells (RBCs) compensates for the defective or reduced adult hemoglobin (Hb) in patients with SCD and beta-thalassemia. HbF is a form of the oxygen carrying Hb that is naturally present at birth and is then replaced by the adult form of hemoglobin.
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