Recombinant hemoglobins as blood substitutes: a biotechnology perspective

Human hemoglobin can be produced in microbial and mammalian organisms using many different expression systems. It is anticipated that recombinant hemoglobins (or globin genes) will have many applications including as an infectious agent-free, inexpensive raw material for a red blood cell substitute, as a vehicle for expression or delivery of other biomolecules, and in gene therapy of inherited hemoglobinopathies. Recombinant expression, combined with site-directed mutagenesis, is facilitating the modification of the functional properties of hemoglobin. Although a functional hemoglobin molecule can be derived using many of the known expression systems, the choice of the production system for manufacturing depends on the scale, acceptable cost, and the associated environmental impact of the various processes. While the efficient bacterial production systems yield a modified, "surrogate" hemoglobin, the transgenic animal-derived product is virtually identical to the human erythrocyte-derived hemoglobin. Both the microbial fermentation, and the mammalian transgenic systems can be geared to produce the enormous quantities of hemoglobin expected to be required to meet the anticipated demand for a successful blood substitute in the future.