title: A human recombinant haemoglobin designed for use as a blood substitute.
abstract: The need to develop a blood substitute is now urgent because of the increasing concern over blood-transmitted viral and bacterial pathogens. Cell-free haemoglobin solutions and human haemoglobin synthesized in Escherichia coli and Saccharomyces cerevisiae have been investigated as potential oxygen-carrying substitutes for red blood cells. But these haemoglobins cannot be used as a blood substitute because (1) the oxygen affinity in the absence of 2,3-bisphosphoglycerate is too high to allow unloading of enough oxygen in the tissues, and (2) they dissociate into alpha beta dimers that are cleared rapidly by renal filtration, which can result in long-term kidney damage. We have produced a human haemoglobin using an expression vector containing one gene encoding a mutant beta-globin with decreased oxygen affinity and one duplicated, tandemly fused alpha-globin gene. Fusion of the two alpha-globin subunits increases the half-life of this haemoglobin molecule in vivo by preventing its dissociation into alpha beta dimers and therefore also eliminates renal toxicity.
authors.affiliation: Somatogen Inc., Boulder, Colorado 80301.
authors.forename: D
authors.initials: D
authors.lastname: Looker
authors.forename: D
authors.initials: D
authors.lastname: Abbott-Brown
authors.forename: P
authors.initials: P
authors.lastname: Cozart
authors.forename: S
authors.initials: S
authors.lastname: Durfee
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: A J
authors.initials: AJ
authors.lastname: Mathews
authors.forename: J
authors.initials: J
authors.lastname: Miller-Roehrich
authors.forename: S
authors.initials: S
authors.lastname: Shoemaker
authors.forename: S
authors.initials: S
authors.lastname: Trimble
authors.forename: G
authors.initials: G
authors.lastname: Fermi
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000009:adverse effects; D003460:Crystallization; D004926:Escherichia coli / Q000235:genetics; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006207:Half-Life; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D046911:Macromolecular Substances; D015394:Molecular Structure; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D005914:Globins; D010100:Oxygen