CRISPR/Cas9 gene editing technology played an instrumental role in the technological breakthrough, but the successful drug development would not have been possible without discoveries in the basic genetics research that identified BCL11A gene, located on chromosome 2, as a suppressor of fetal hemoglobin (Hb F), located on chromosome 11, by physician-scientists at Boston Children’s Hospital and at the National Institute of Health (NIH).18
A molecular obstacle must first be cleared for the hemoglobin gene to be successfully transcribed and translated to functional oxygen-binding molecules. The obstacle gene is called BCL11A, which suppresses fetal hemoglobin (Hb F). Of note, the Hb F blood level in the body begins to decrease around six months of age. Adults mainly express adult hemoglobin (Hb A), although a low level of Hb F of less than ~0.6–0.8% continues to exist.
18. Basak, A., Hancarova, M., Ulirsch, J. C., Balci, T. B., Trkova, M., Pelisek, M., Vlckova, M., Muzikova, K., Cermak, J., Trka, J., Dyment, D. A., Orkin, S. H., Daly, M. J., Sedlacek, Z., & Sankaran, V. G. (2015). BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations. The Journal of clinical investigation, 125(6), 2363–2368. https://doi.org/10.1172/JCI81163
