Network of potential targets for genome-editing–based therapy of the β-globin disorders. Therapeutic genome-editing strategies rely on genetic correction through the HDR pathway or genetic disruption through the NHEJ pathway. Genetic correction/repair strategies involve direct modification of the β-globin gene cluster through (1) correction of the sickle mutation in the β-globin gene or (2) insertion of the HPFH-associated single-nucleotide polymorphisms (SNPs) into the Gγ or Aγ promoters. Genetic disruption strategies involve targeted disruption of (1) BCL11A coding sequence, (2) the minimal critical sequences in the +58 DHS within the erythroid-specific BCL11A enhancer, (3) the HbF-associated sequences within the Aγ-δ intergenic region, or (4) other genes with a known role in γ-globin regulation such as MYB, KLF1, LRF/ZBTB7A, or EHMT1/EHMT2. HbA, adult hemoglobin.