Mechanism of action
ZYNTEGLO® can address the underlying genetic cause of beta-thalassemia by adding functional copies of a modified β-globin gene to the patient’s own hematopoietic stem cells (HSCs).1
Modified β-globin expression is designed to correct the α/β-globin imbalance and enable the production of a modified functional HbA (HbAT87Q).1
- HbAT87Q has a nearly identical structure and similar oxygen affinity to naturally occurring HbA.2,3
BB305 LVV, a replication-incompetent lentiviral vector (LVV), carries a modified β-globin gene (βA-T87Q-globin gene).1
ZYNTEGLO is manufactured by adding functional copies of the βA-T87Q-globin gene to the patient’s own HSCs ex vivo via transduction of autologous CD34+ cells with BB305 LVV.1
*The BB305 LVV promoter, a regulatory element of the LVV that controls the expression of the transgene selected for BB305 LVV, is a cellular (non-viral) promoter that controls gene expression specific to the erythroid lineage cells (red blood cells and their precursors).1
After infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce RBCs containing biologically active βA-T87Q-globin.1
Analogous to endogenous β-globin, βA-T87Q-globin pairs with α-globin to produce functional HbA derived from ZYNTEGLO (HbAT87Q).1
ZYNTEGLO has the potential to increase functional HbA and total Hb to normal levels, eliminating the dependence on regular RBC transfusions.1
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