Definition

A preparation of autologous, CD34-positive hematopoietic stem cells (HSCs), obtained from patients with sickle cell disease (SCD), transduced ex vivo with the BB305 recombinant replication-defective, self-inactivating lentiviral vector (LVV) encoding for an engineered, modified form of human beta-globin (hemoglobin-beta, HBB) gene, beta-A-T87Q (b-A-T87Q), in which the threonine (Thr; T) at position 87 has been substituted with glutamine (Gln; Q), with potential to restore beta-globin expression and function in SCD patients. Autologous CD34-positive stem cells are isolated from the patient’s own bone marrow and the cells are transduced with the lentiviral vector. Upon re-infusion of autologous bb1111 back into the patient, these cells express the non-sickling b-A-globin protein b-A-T87Q-globin, thereby allowing the body to make anti-sickling hemoglobin, HbA-T87Q, and thus normal, healthy red blood cells (RBCs). Beta-globin, the beta-chain of the most common form of hemoglobin, is encoded by the HBB gene; mutations in this gene prevent normal beta-globin production and are associated with SCD. The b-A-T87Q form of beta-globin has increased anti-sickling activity compared to the wild type protein.