Table 1.

Potential targets for therapeutic genome editing for the β-globin disorders

Target	Repair strategy	Efficiency	Advantages/Disadvantages
Repair of SCD allele	HDR	Low-moderate	Single target allele; inadvertent generation of β-thalassemia alleles
Repair of β-thalassemia allele	HDR	Low-moderate	Heterogeneous target alleles
Recreation of nondeletional HPFH	HDR	Low-moderate	Inadvertent generation of γ-null alleles; identified HPFH patients support mutation tolerance/clinical benefit
Recreation of deletional HPFH	NHEJ	Low-moderate	Insufficient efficiency of targeted deletion; identified HPFH patients support mutation tolerance/clinical benefit
Other targets in β-globin cluster	NHEJ	—	Targets unknown
BCL11A	NHEJ	High	HSC/B-cell dysfunction due to BCL11A requirement; haploinsufficient patients have significant HbF induction
BCL11A enhancer	NHEJ	High	Erythroid-specific BCL11A loss; haploinsufficient patients have significant HbF induction
α-Globin	NHEJ	Moderate-high	Balance α-β chains; inadvertent generation of α-thalassemia cells
KLF1	NHEJ	High	Broad role in cell proliferation and cellular development
MYB	NHEJ	High	Broad role in cell proliferation and cellular development
LRF/ZBTB7A	NHEJ	High	Broad role in cell proliferation and cellular development
EHMT1/EHMT2	NHEJ	High	Role in hematopoiesis unknown
LIN28B pathway	NHEJ	High	Role in hematopoiesis unknown