Hemoglobinopathies: from Sickle Cell Disease to Beta Thalassemia
Mutations in the adult beta-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and beta thalassemia. Previous studies have shown that the activation of gamma globin — the subunit of fetal hemoglobin — can ameliorate the symptoms of sickle cell disease and beta thalassemia.
A 3D View of the Genome
Using CRISPR-Cas9, Dr. Zhang’s team found that 3’HS1 deletion induces the gamma-globin gene activation and alteration of chromosomal loops in the beta-globin locus. Specifically, 3’HS1 deletion incorporates an insulated enhancer to activate the gamma-globin gene.
A Target for Gene Therapy
Altering the CTCF binding profile across the locus can significantly change the expression of the β-globin genes, suggesting that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.