On April 3, 2023, Vertex Pharmaceuticals and CRISPR Therapeutics announced the completion of the rolling biologics license application (BLAs) to the FDA for Exa-cel, intended for the treatment of sickle cell disease (SCD) and beta-thalassemia (TDT). Exa-cel is poised to become the world’s first approved CRISPR gene editing therapy.
Fetal hemoglobin (HbF, α2γ2) is a form of hemoglobin present during embryonic development. After birth, the BCL11A regulatory factor binds to the promoter and suppresses the expression of gamma-globin, gradually replacing HbF with adult hemoglobin (HbA, α2β2). Patients with SCD and TDT exhibit abnormal expression of beta-globin, and gene editing techniques can reactivate HbF expression. Exa-cel utilizes CRISPR-Cas9 gene editing technology to modify the BCL11A gene in the patient’s CD34+ cells in vitro, which are then infused back into the body to increase HbF expression, thereby achieving the therapeutic goal.