Definition

A population of autologous cluster of differentiation 34 (CD34)-positive human hematopoietic stem and progenitor cells (HSPCs) ex-vivo base-edited with fusions of a deaminase and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas ribonucleoprotein, with potential usage for transplantation in patients with sickle cell disease (SCD). CD34-positive HSPCs are isolated from human blood upon apheresis and are genetically modified and base-edited ex vivo to disrupt the HBG1/HBG2 gene promoter motif bound by the transcriptional repressor B-cell lymphoma/leukemia 11A (BCL11A) gene. This increases the expression of fetal hemoglobin (HbF) and inhibits hemoglobin S (HbS) polymerization in erythrocytes that differentiate from BEAM-101. Upon infusion back into the patient following myeloablative, conditioning chemotherapy, BEAM-101 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. 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.