Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.

Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells.

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality .