Hemoglobinopathies

Our gene-editing approach aims to treat β-thalassemia and sickle cell disease by increasing fetal hemoglobin, an approach supported by well-understood genetics

The inherited hemoglobinopathies β-thalassemia and sickle cell disease (SCD) result from mutations in a gene that encodes a key component of hemoglobin, the oxygen carrying molecule in blood. Both diseases currently require lifetime treatment that can result in the need for regular transfusions, painful symptoms and chronic hospitalizations. Both of these diseases result in reduced life expectancy.

Our approach to treat β-thalassemia and SCD is designed to increase levels of fetal hemoglobin (HbF), a naturally-occurring form of hemoglobin present in all people before birth. HbF can substitute for the diseased hemoglobin in β-thalassemia and SCD patients, reducing or eliminating symptoms.

Symptoms in β-thalassemia and SCD arise as hemoglobin switches from fetal to adult

In most people, levels of HbF begin to decline in the months preceding birth, while levels of adult hemoglobin (HbA) increase. Since only HbA contains the component of hemoglobin defective in patients with β-thalassemia or SCD, these patients do not begin to experience symptoms until several months after birth, once hemoglobin switching has occurred.

Hereditary persistence of fetal hemoglobin reduces symptoms

Rare individuals continue to express HbF into adulthood, a benign condition known as Hereditary Persistence of Fetal Hemoglobin (HPFH). β-thalassemia and SCD patients with HPFH have reduced disease symptoms, or no symptoms at all, because fetal hemoglobin can substitute for the diseased adult hemoglobin.

Our lead therapeutic program, Exa-cel, aims to increase fetal hemoglobin expression by editing patients' own blood stem cells with CRISPR/Cas9

As a therapy, Exa-cel involves isolating a patient’s own blood stem cells, editing them with CRISPR/Cas9 to increase HbF expression, and then returning the edited cells to the patient. We believe that over time these edited blood stem cells will generate red blood cells that have increased levels of HbF, which may reduce or eliminate patients’ symptoms. In 2017, we signed an agreement to co-develop and co-commercialize this program with our partner Vertex Pharmaceuticals.