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Artificial Haemoglobin - Blood Substitute for Substituting Blood
Human haemoglobin is available in abundance. It is also one of the most sought after protein available. Haemoglobin has been studied so extensively that all the properties and expression mechanisms is well known. This makes it easier to develop haemoglobin artificially (blood substitute) to fulfil the rising demand of haemoglobin.

Mechanism involved:
Human haemoglobin basically consist of two parts mainly heme and globin. The heme portion of the protein is common among many organisms. This property can be exploited to produce haemoglobin artificially by using recombinant DNA technology. In the production of recombinant haemoglobin, only the globin part needs to be integrated and expressed. Since it naturally produces the heme part, this proves to be an easy method to produce active haemoglobins. As in such host animals the native haemoglobin serves the similar function, recombinant protein is successfully expressed.

Different organisms serve as hosts to haemoglobin production. This include

Microbial host: In microbes, the gene encoding the heme part, which produces heme identical to human haemoglobin, is first isolated and purified and then combined with globin structure isolated from human blood. Thus a proper functional haemoglobin gene is inserted in vitro into a microbial cell and the expression of the same releases haemoglobin into the cell. This haemoglobin, produced inside a microbial system, can be easily isolated and purified. The major disadvantages involved are the high cost of production involved in this technique.

Mammalian host:
The haemoglobin production in mammals involves production of transgenic animals. The genome of such animals is integrated with genes responsible for production of haemoglobin. In this technique, it is possible to determine the amount of haemoglobin genes to be expressed by controlling the genome of transgenic animals. Thus the expression levels can also be easily regulated to increase or decrease production. The main disadvantage of the process is time required to produce actual results.

The main function of blood with respect to natural haemoglobin is to act as a carrier for oxygen. Apart from this, blood also exhibits several other functions like immunity by white blood cells, blood clotting by platelets, electrolyte balance, and several other functions by blood proteins. The blood substitute is expected to fulfil some properties of blood if not all. Research corresponding to production of actual blood compiling various functions of blood is also initiated.

Advantages of blood substitute
(i) High production rate:
By producing blood substitutes, it is possible to supply blood as the demand arises.
(ii) Production of haemoglobin exhibiting specific characteristics:
As a result of rDNA technology, the recombinant haemoglobin produced exhibit several desired properties.
(iii) In depth analysis of blood related disease: since the blood substitute resembles haemoglobin closely, the study of mutations or disease affecting haemoglobin can be studied buy inducing such defects in the blood substitute.
(iv) Gene therapy:
The defective gene responsible for certain diseases like anaemia and thalassemia can be treated by gene therapy. It is also a proposed cure for inherited hemoglobinopathy
(v) Protein delivery: It can also acts as a carrier for certain biomolecules like proteins.
(vi) Safe blood transfusion: Blood substitute can be used in the place of blood for transfusion. Since it is produced artificially under sterile conditions, safe and infectious free blood can be transfused to affected people.

(i) Renal toxicity: Filtration of blood with blood substitute particles has found to affect kidneys adversely. As a result, cases which indicate renal toxicity in persons with blood substitutes is reported.
(ii) Other side affects like hypertension, fatigue is also known
(iii) This is also known to induce heart attacks.
(iv) Since animal and human haemoglobin share many properties, the separation of recombinant protein from animal ones after production proves to be difficult.
(v) It is not economical to produce on larger scale.
(vi) It is less stable and has to be transfused immediately rather than normal blood which has extended shelf life, comparatively.

Future prospects:
The stem cell research has been suggested as a very prospective area wherein the human haemoglobin can be isolated in its natural form and developed on larger scale. The haemoglobin protein can be isolated from stem cells collected and cultured to produce the same under invitro conditions. Since in this technology, the human haemoglobin is isolated in its original form, complexities due to a foreign substance in the body does not arise. All the vital functions of blood will be fulfilled by blood produced by stem cell technology.
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