Figure 2.
Genome-editing–based strategies for the treatment of β-hemoglobinopathies. (A) HDR-based approaches use nucleases or peptide nucleic acids (PNAs) and a donor template to correct the disease-causing mutation (eg, the SCD mutation). (B) BCL11A downregulation (via the NHEJ-mediated disruption of a GATA1 binding site in the +58-kb erythroid-specific enhancer) leads to γ-globin reactivation. (C) Mimicking HPFH mutations in the γ-globin promoter (Prom) (eg, the 13-bp deletion) through NHEJ and MMEJ leads to γ-globin reactivation, probably via BCL11A eviction. Reproducing large HPFH deletions via NHEJ (eg, HPFH-5) induces γ-globin expression. (D) Reducing α-globin expression (via the NHEJ-mediated deletion of the R2 α-globin enhancer) improves the α-/non-α-globin ratio in β-thalassemia. chr, chromosome; ex, exon.

Genome-editing–based strategies for the treatment of β-hemoglobinopathies. (A) HDR-based approaches use nucleases or peptide nucleic acids (PNAs) and a donor template to correct the disease-causing mutation (eg, the SCD mutation). (B) BCL11A downregulation (via the NHEJ-mediated disruption of a GATA1 binding site in the +58-kb erythroid-specific enhancer) leads to γ-globin reactivation. (C) Mimicking HPFH mutations in the γ-globin promoter (Prom) (eg, the 13-bp deletion) through NHEJ and MMEJ leads to γ-globin reactivation, probably via BCL11A eviction. Reproducing large HPFH deletions via NHEJ (eg, HPFH-5) induces γ-globin expression. (D) Reducing α-globin expression (via the NHEJ-mediated deletion of the R2 α-globin enhancer) improves the α-/non-α-globin ratio in β-thalassemia. chr, chromosome; ex, exon.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal