Hemoglobin-based Artificial Blood

 The development of blood substitutes has been intensified due to the increased prevalence of blood-borne infections including hepatitis and human immunodeficiency virus (HIV).  Although hemoglobin and non-hemoglobin products have been developed in order to deliver oxygen and sustain life, problems remain with the products' safety and efficiency.  Free unmodified hemoglobins cannot be used as a blood substitute because (1) a large number of hemoglobin dimers via the dissociation of free hemoglobins will damage the kidney, (2) hemoglobins without 2,3-diphosphoglycerate will reduce their ability to unload suitable oxygen in the tissue, (3) free hemoglobins will scavenge nitric oxide to cause hypertension, and (4) lack of reduction and superoxide-scavenger systems maintain the O₂ binding capacity and avoid oxidative stress. We have developed polyethyleneglycol (PEG) - and genetically modified hemoglobins as a blood substitute.  The ends of PEG are linked to a peptide modulator and hemoglobin, respectively.  PEG-conjugated hemoglobin will reduce renal filtration and prevent kidney damage via the size increase of the hemoglobin molecule.  The modulator will bind with deoxyhemoglobin and can unload appropriate oxygen from oxyhemoglobin in the tissue.  This is a novel approach to developing hemoglobin as a blood substitute and hopefully can be applied in blood transfusion in the future.