Development of Recombinant Hemoglobin-Based Oxygen Carriers

作者: Cornelius L. Varnado , Todd L. Mollan , Ivan Birukou , Bryan J.Z. Smith , Douglas P. Henderson

DOI: 10.1089/ARS.2012.4917

关键词: Recombinant DNABiochemistryHemeChemistryProtein subunitHeminHemoglobinWhole bloodTransfusion therapyEscherichia coli

摘要: Abstract Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole and packed red cells use in transfusion therapy. One such alternative involves the of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts human Hb can be expressed purified from transgenic Escherichia coli. physiological suitability this material enhanced using protein-engineering strategies address specific efficacy toxicity issues. Mutagenesis (i) adjust dioxygen affinity over 100-fold range, (ii) reduce nitric oxide (NO) scavenging 30-fold without compromising binding, (iii) slow rate autooxidation, (iv) hemin loss, (v) impede subunit dissociation, (vi) diminish irreversible denaturation. Recombinant production is potentially unlimited readily subjected current good manufacturing practices, but may restricted by cost. Ac...

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