CASGEVY

Exagamglogene autotemcel is a cell therapy consisting of autologous CD34+ HSPCs ex vivo edited by CRISPR/Cas9-technology. The highly specific guide RNA enables CRISPR/Cas9 to make a precise DNA double-strand break at the critical transcription factor binding site (GATA1) in the erythroid specific enhancer region of the BCL11A gene. As a result of the editing, GATA1 binding is irreversibly disrupted and BCL11A expression reduced. Reduced BCL11A expression results in an increase in γ-globin expression and foetal haemoglobin (HbF) protein production in erythroid cells, addressing the absent globin in transfusion-dependent β-thalassemia (TDT) and the aberrant globin in sickle cell disease (SCD), which are the underlying causes of disease.