CRISPR/Cas deletion of aberrant splice sites provides a novel therapeutic approach for β-thalassemia. Two prevalent β-thalassemia mutations are illustrated in the human β-globin gene: IVS2-654C>T, which produces an aberrant splice donor site in IVS2, and IVS1-110G>A, which produces an aberrant splice acceptor site in IVS1. Additional sequences necessary for efficient splicing are also indicated. Xu et al demonstrate that electroporation of CD34⁺ HSPCs with ribonucleoproteins composed of Cas9 or Cas12a protein and guide RNAs complementary to the IVS1 or IVS2 mutations significantly increase the level of correctly spliced β-globin mRNA and, consequently, the amount of HbA produced in red blood cells after in vitro differentiation.