Base editing for fetal hemoglobin expression in sickle cell disease

A-to-G base editing of the HBG1 promoter to replicate a benign variant seen in individuals with hereditary persistence of fetal hemoglobin could help treat sickle cell disease by inducing expression of fetal hemoglobin to compensate for dysfunctional adult hemoglobin.

Five methods for inducing expression of γ-globin, a component of fetal hemoglobin encoded by HBG1and HBG2, were compared — CRISPR-Cas9 targeting of either the HBG1 enhancer BCL11A or the binding site of BCL11A in the HBG1 promoter, or adenine base editing to create three different variants in the HBG1 promoter found in hereditary persistence of fetal hemoglobin, which create binding sites for erythroid transcriptional activators. ...