We show that in beta-thalassemia iPSCs, this CRISPR activation approach permits accurate modeling of a beta-thalassemia splice junction mutation in HBB, similar to what was previously shown in HeLa cells overexpressing the beta-globin gene with the IVSII-1 G > A mutation (Treisman et al., 1982), and facilitates ready identification of restored RNA processing in corrected cells. Here, HBB is linked to beta thalassemia.