ABOUT

HaemO2 is a synthetic biology project based at the University of Essex, UK, that is developing a third generation artificial blood substitute.

OUR AIMS

Hemoglobin is the key protein in red blood cells that carries oxygen around our bodies. A haemoglobin-based oxygen carrier (HBOC) could be used as a substitute for blood lost in surgery or trauma, but to date attempts to make a safe and effective HBOC have proved problematic. The redox activity of heme iron, when outside the safe confines of the red blood cell, is considered a key problem when attempting to engineer a safe (HBOC).

ENGINEERING

The HaemO2 project has been funded to engineer recombinant hemoglobin variants with enhanced electron transfer pathways to solve this problem.

“HaemO2 is all about using the tools of modern synthetic biology to create a safe blood substitute for the 21st century”

The variants will be better able to detoxify the reactive high oxidation state iron and free radicals produced in extracellular haemoglobin under conditions of oxidative stress. The novel proteins will therefore form a key component of our blood substitute product.

Our first goal is to produce an artificial blood substitute that can be used for: high-risk patients; high stress environments; immunocompromised or chemotherapy patients; and patients where standard donor blood carries a risk including patients who have had previous transfusion related adverse events.

TECHNOLOGY

A number of companies have attempted to develop alternatives to transfusions, generally based on modifications of the red cell oxygen transport protein hemoglobin. However, toxic side effects have been seen in a range of clinical trials. Therefore no product is currently licensed for use in the major healthcare markets of the world.

INTRINSIC TOXICITY

The “intrinsic toxicity” of the hemoglobin molecule is likely to be responsible for these side effects. Oxidative stress produces highly reactive “ferryl” intermediates at the heme iron and free radicals elsewhere in the protein.

“Engineering a range of hemoglobin molecules that are less likely to induce oxidative damage.”

At the University of Essex basic science funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) has revealed that introducing specific amino acid residues (tyrosine) on the hemoglobin protein can detoxify the protein. This is achieved by enabling the body’s own defences - vitamin C and uric acid - to better reduce the potentially damaging oxidative intermediates.

LESS DAMAGE

The University of Essex has engineered a range of novel hemoglobin molecules that have additional tyrosine residues; consequently they are less likely to induce oxidative damage. Patents have been granted in the USA and Australia and are pending in other territories.