Biologic
RCSB PDB 4CMP
Exagamglogene autotemcel
Casgevy
- Mechanism of action
- CRISPR-Cas9 gene-edited autologous hematopoietic stem cells (BCL11A enhancer disruption)
- In plain language
- Uses CRISPR molecular scissors to edit a switch in your own stem cells, turning fetal hemoglobin production back on to treat sickle cell disease and beta-thalassemia.
- How it works
- Exagamglogene autotemcel is an ex vivo CRISPR/Cas9 gene-edited autologous CD34+ hematopoietic stem cell product. Patient stem cells are collected by apheresis, then a CRISPR/Cas9 complex creates a double-strand break at the erythroid-specific enhancer region of the BCL11A gene, disrupting a binding motif required for BCL11A expression. Reduced BCL11A in the erythroid lineage de-represses gamma-globin transcription, increasing fetal hemoglobin production. The edited cells are infused back into the patient after myeloablative conditioning, engrafting to provide durable fetal hemoglobin elevation.
- Therapeutic applications
- Indicated for patients 2 years and older with sickle cell disease and recurrent vaso-occlusive crises, or with transfusion-dependent beta-thalassemia requiring frequent red blood cell transfusions.
- Class
- CRISPR gene-editing therapy
- Therapeutic area
- Hematology (sickle cell disease / beta-thalassemia)
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