www.checkbiotech.org www.raupp.info

Human serum albumin (HSA) is the intravenous protein most commonly used
in the world for therapeutic ends, March 2006.

It is employed to stabilise blood volume and to avoid risk of a heart
attack, its administration in operating theatres being almost a daily
occurrence. It is used for haemorrhages, burns, surgical operations or
when the patient shows symptoms of malnutrition or dehydration, chronic
infections and renal or liver illnesses. The annual consumption in Spain
is about 10 tons but, at a worldwide level, the demand exceeds 500 tons.

Agricultural engineer, Alicia Fernández San Millán, has developed a
novel technique in Spain - plastidial transformation, in order to
produce, in a recombinant form, human albumin from tobacco plants.
According to her PhD thesis, plastidial transformation is an
economically viable alternative, as it enables increasing the levels of
HSA by between 10 and a 100 times, compared to levels obtained by
nuclear transformation.

The title of the PhD is: ?Production of human serum albumin in tobacco
plants by means of plastidial transformation?. It should be added that
this novel technique, fruit of Ms Fernández San Millán?s PhD, has been
patented at a world level and there is already a company interested in
marketing it.

An efficacious and cheap alternative

Commercial albumin is currently extracted from blood, but the lack of
sufficient reserves to cover all worldwide needs has instigated
researchers to look for new formulae to multiply this protein. One of
the methods most used has been the obtention of HSA from yeasts and
mammal cells. However, their high market-place costs have meant that
these methods are not competitive. While the price at the pharmacy of
albumin produced using plasma is 4 euros per gram, that obtained from
yeasts or mammal cells costs between 300 and 4,000 euros per gram.
Another option worked on over recent years has been the production of
albumin from vegetables, always using nuclear transformation.

The novelty in this research arises from the method of obtention of the
HSA. The plastidial system enables the extraction of great quantities of
albumin. With nuclear transformation, the maximum level obtained is 0.5%
of the total soluble protein of the plant, while application of the
plastidial system multiplies this percentage by fourteen (to 7%),
reaching an average of 0.9 milligrams of HSA per gram of fresh leaf
weight.

The key is the place where the gene in question is deposited. With the
nuclear transformation method, it integrates into the DNA of the cell
nucleus of the leaf and, thus, can only manage a small number of copies
of the gene. With the plastidial system, on the other hand, the gene is
introduced into the chloroplast, where photosynthesis takes place and
where the genomes can multiply up to 10,000 times.

A property highly valued by the experts has to be added to these
positive results: the production of albumin from plants using this
technique does not involve the escape of genes through pollen
transmission given that, with most crops under cultivation, the genome
of the plastids is inherited maternally.

More biomass in tobacco plants

The tobacco plant is very easy to handle genetically and also it is
great generator of biomass. The authoress of the thesis says that up to
100 tons of biomass per hectare can be obtained in optimum growth
conditions. ?Given that the protein is produced in the chloroplasts, the
more the leaf biomass we have, the more albumin we can get?.

To date all the trials undertaken with tobacco plants have been with
laboratory varieties. The aim is to do tests with commercial varieties.
Laboratory plants are very small and, as a result, the quantity of
albumin extracted is not sufficient. However, the commercial varieties
of tobacco are some 30 times more productive in terms of biomass.

Despite the advantages demonstrated by the experts, there is still a
long way to go. Involving, as it does, a protein that is intravenously
injected into patients, it has to be thoroughly purified to eliminate
any kind of contaminant. Moreover, it is necessary to assure that the
protein obtained has an identical structure to the human one to
guarantee that its functioning will be 100%.

[www.basqueresearch.com]

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