Hemoglobinopathies

Lead Indication Approach Program Research Preclinical Phase 1/2 Phase 3
ZFN (knockout) Bioverativ
Research Phase complete
Preclinical Phase in progress
Phase 1/2 Phase not started
Phase 3 Phase not started

Beta thalassemia is a blood disease caused by a mutation in the beta-globin gene that results in greatly impaired production of healthy red blood cells. In collaboration with Bioverativ, we are developing cell therapies for both sickle cell disease and beta thalassemia based on the use of our ZFN genome editing technology to modify a patient’s own (autologous) hematopoietic stem cells (HSCs).

ZFN (knockout) Bioverativ
Research Phase complete
Preclinical Phase in progress
Phase 1/2 Phase not started
Phase 3 Phase not started

Sickle cell disease is a blood disease caused by a mutation in the beta-globin gene that causes the red blood cells to form an abnormal sickle or crescent shape. The cells are fragile and deliver less oxygen to the body’s tissues resulting in pain and irreversible organ damage. In collaboration with Bioverativ, we are developing cell therapies for both sickle cell disease and beta thalassemia based on the use of our ZFN genome editing technology to modify a patient’s own (autologous) hematopoietic stem cells (HSCs).

About beta thalassemia and sickle cell disease

Sickle cell disease (SCD) and beta thalassemia are inherited blood disorders caused by mutations in the gene encoding beta-globin, a vital part of the oxygen-carrying hemoglobin complex in red blood cells (RBCs). The mutation that causes beta thalassemia results in impaired production of healthy red blood cells, leading to life-threatening anemia, enlarged spleen, liver and heart, and bone abnormalities. The mutation in SCD causes the RBCs to form an abnormal sickle or crescent shape which makes them fragile and less capable of delivering oxygen to tissues. They can also get stuck more easily in small blood vessels and break into pieces that can interrupt healthy blood flow which further decrease the amount of oxygen flowing to tissues. Almost all patients with SCD have painful vaso-occlusive crises, which can cause irreversible organ damage.

It is estimated that about 420 million people are carriers for the disease

~300,000

Babies are born with severe hemoglobin disorders every year

According to the World Health Organization (WHO) in 2011

~ 5%

Of the world’s population carries trait genes for hemoglobin disorders, mainly, sickle cell disease and thalassemia

According to the World Health Organization (WHO) in 2011

~1000

People in the United States with beta-thalassemia major

According to the Centers for Disease Control and Prevention (CDC)

~100,000

People in the United States with sickle cell disease

According to the Centers for Disease Control and Prevention (CDC)

Our Therapeutic Approach

With our collaborators, Bioverativ, the blood disorder focused spin-off of Biogen, we are developing a ZFN-mediated gene knockout approach for use in a patient’s own hematopoietic stem cells (HSCs) as a potential single-administration long-lasting option for both SCD and beta thalassemia. These programs are currently in preclinical development.

In HSPCs, our genome editing technology can be used to precisely disrupt the erythroid-specific "enhancer" of BCL11A expression, a regulatory DNA sequence in the genome that is essential for expression of BCL11A, a key transcriptional regulator that controls the switch from expression of the functional fetal gamma-globin to expression of the mutant adult beta-globin.  Knocking out the enhancer reduces or eliminates the expression of BCL11A and enables the continued production of therapeutic fetal globin.