More than 10 million red blood cell (RBC) transfusions are performed annually in the United States alone, making it one of the most popular medical therapies. However, for transfusion efficacy and safety, alloimmunization to foreign Rh proteins (RhD and RhCE) on donor RBCs continues to be problematic. 

Patients with sickle cell illness who often get blood transfusions and have a significant genetic variation in the Rh blood group system are disproportionately affected by alloantibody formation. The absence of suitable reagent RBCs with rare Rh antigen morphologies made it difficult to identify Rh antibody targets precisely, even if hundreds of RH variations are already recognized. Researchers created a renewable source of cells with distinctive Rh profiles using a mix of human induced pluripotent stem cell (iPSC) reprogramming and gene editing to make it easier to identify complicated Rh antibodies. They created an extremely unusual Rh null iPSC line that is deficient in both RHD and RHCE

In the Rh null background, any combination of RHD or RHCE complementary DNAs might be reintroduced by targeting the AAVS1 safe harbor locus to produce RBCs that express certain Rh antigens like RhD alone (labeled D–), Goa+, or DAK+. The RBCs produced from these iPSCs (iRBCs) can accurately assess the specificity of Rh antibodies in patient plasma and are compatible with widely used laboratory techniques. 

Rh-engineered iRBCs can serve as a simple diagnostic tool and serve as a blueprint for future initiatives to provide a different supply of uncommon RBCs for alloimmunized individuals.