MECHANISM OF ACTION

By using a patient’s own cells, ZYNTEGLO gives patients the potential to achieve transfusion independence without the need for a donor1

Patients with transfusion-dependent β-thalassaemia (TDT) live with severe anaemia, and are dependent on lifelong blood transfusions for survival. Chronic transfusions lead to iron overload, and can result in serious comorbidities and reduced survival. TDT is the most severe form of β-thalassaemia.3,4,5

ZYNTEGLO is a genetically modified autologous CD34+ cell–enriched population that contains haematopoietic stem cells (HSCs) transduced with lentiviral vector (LVV) encoding the βA-T87Q-globin gene.1

Following successful engraftment and achievement of transfusion independence, the effects of ZYNTEGLO are expected to be life-long.1

Mechanism of action: addressing the underlying genetic cause of TDT1

Diagram of BB305 LVV carrying the Beta AT87Q-globin gene

BB305 LVV, used to manufacture ZYNTEGLO, is a replication-incompetent, self-inactivating LVV that carries the βA-T87Q-globin gene (a modified β-globin gene)1

BB305 LVV approaching patient's HSC to deliver Beta AT87Q-globin gene

ZYNTEGLO adds functional copies of the βA-T87Q-globin gene to the patient’s own HSCs ex vivo via transduction of autologous CD34+ cells with BB305 LVV1

Transduced CD34+ HSC producing RBCs with the modified haemoglobin, HbAT87Q

Transduced CD34+ HSCs engraft in the patient's bone marrow to produce RBCs with functional Hb that contains βA-T87Q-globin (HbAT87Q)1


βA-T87Q-globin expression is designed to correct the β/α-globin imbalance in erythroid cells and has the potential to increase total Hb to normal levels.1