Figure 6.

Elevating HbF levels by distinct genome editing approaches.

A: Traditional Cas9 or base editors can be used to either disrupt the BCL11A binding motif upstream of the γ-globin promoters (top) or the erythroid-specific BCL11A enhancer (bottom). B: Disruption of the BCL11A binding motif displaces BCL11A, allowing the activating locus control region (LCR) access to the γ-globin promoters. C: Creating indels or base substitutions in the BCL11A enhancer decreases expression of BCL11A specifically in the erythroid lineage, which also allows the LCR access to the γ-globin promoters.