Blood transfusions provide important medical benefits primarily centered on the replacement of lost blood in trauma and surgical patients.
However, the availability of blood transfusions in both hospital and field settings is limited by the safety and availability of the donated blood supply. Therefore, blood substitutes have long been sought as one way to alleviate these safety and availability concerns.
To date, current blood substitutes have met with modest clinical success against a backdrop of varied concerns regarding cardiac function, renal toxicity, and molecular stability. Recombinant oxygen-binding heme proteins incorporating circularly permuted globins address these issues through the promotion of cross-linking and the formation of hemoglobin multimers.
Recombinant DNA sequences coding for the hemoglobin protein have been modified to introduce new peptide linkers and termini. The resulting genetic cross-linking and covalent binding promote stability within individual hemoglobin molecules and the formation of high-weight hemoglobin multimers.
Applications
- As a blood substitute in the treatment of traumatic injury in both hospital and field settings
Benefits
- Increased safety and availability of blood substitutes for transfusion
- Potential for increased stability and reduced toxicity in a recombinant protein due to the modifications that promote subunit cross-linking and the formation of hemoglobin multimers