Preferred Label : Autologous CRISPR-Cas9 Modified/BCL11A Gene-disrupted Human Hematopoietic Stem and
Progenitor Cells OTQ923;
NCIt synonyms : Autologous BCL11A Gene-disrupted HSPCs OTQ923; Autologous CRISPR-Cas9 Genetically-modified HSPCs OTQ923;
NCIt definition : 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.;
Molecule name : OTQ 923; OTQ-923;
NCI Metathesaurus CUI : CL1412671;
Origin ID : C175342;
UMLS CUI : C5446452;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
