TF and sickle cell disease: Within the latter subset, the most interesting and technically feasible from the perspective of developing a new therapy were considered to be ceruloplasmin (for aceruloplasminemia), haptoglobin and hemopexin (for hemoglobin toxicity relevant to sickle cell disease) and transferrin (for β-thalassemia), as preclinical efficacy studies were performed with proteins purified from plasma, representing effective comparators20,23,40–42.