Editing of the BCL11A gene by CRISPR/Cas9 might be a future gene therapy approach to treat sickle cell disease and beta thalassemia. This is suggested by the first results of a pilot study led by clinicians and researchers from Regensburg, Germany, and the U.S., which was published in the New England Journal of Medicine. More than a year after a single administration of the gene-editing therapy, the first two patients showed strongly increased fetal hemoglobin levels, they were symptom-free and no longer needed blood transfusion. Both had high levels of the fetal hemoglobin boosted by BCL11A gene editing in their bone marrow and blood.

Sickle cell disease and beta thalassemia are blood disorders with defective hemoglobin formation due to mutations in the HBB gene, encoding a subunit of adult hemoglobin. They are associated with severe manifestations including repeated strong pain and can lead to a reduced life expectancy. BCL11A is a transcription factor that represses the synthesis of gamma globin, a component of fetal hemoglobin. While the production of fetal hemoglobin normally decreases after birth, the study investigators designed their approach of knocking out BCL11A to reactivate its production.

In the clinical phase I/II study sponsored by pharmaceutical companies CRISPR Therapeutics and Vertex Pharmaceuticals, the researchers harvested hematopoietic stem and precursor cells from their patients and genetically engineered a specific, regulatory enhancer segment of BCL11A. Then they reinfused the cells back into the patients. The same NEJM issue also reports another gene therapy approach targeting BCL11A to treat sickle cell disease. In this second study, researchers used lentiviral vectors and microRNA to block BCL11A production, a strategy which also yielded positive results.