 |
|
Title
|
|
A human recombinant haemoglobin designed for use as a blood substitute.
|
|
|
Authors
|
|
D.Looker,
D.Abbott-Brown,
P.Cozart,
S.Durfee,
S.Hoffman,
A.J.Mathews,
J.Miller-Roehrich,
S.Shoemaker,
S.Trimble,
G.Fermi.
|
|
|
Ref.
|
|
Nature, 1992,
356,
258-260.
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|