Production of biological products: the future belongs to algae!
A large number of therapeutic proteins, including a number of drugs for the treatment of tumors, multiple sclerosis and diabetes, are produced using cultures of bacteria, yeast or mammalian cells. However, such production methods are very expensive in many cases, since a large amount of nutrients is required to maintain the viability of cell lines, and the creation and maintenance of sterile bioreactors requires significant energy and financial investments. Researchers at the University of California at San Diego, working under the leadership of Stephen Mayfield, believe that rapidly multiplying and unpretentious green algae, which have enough sunlight, poor environment and carbon dioxide contained in the air, are an optimal alternative from a financial point of view.
In the article "Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtii", published on March 7 in the preliminary on-line version of Plant Biotechnology Journal, researchers describe experiments in which they embedded in the genome of the green algae chlamydomonas genes providing the production of seven different therapeutic proteins, including interferon, used for the treatment of multiple sclerosis, and proinsulin, used in the treatment of diabetes. Currently, the tested drugs are produced using yeast, bacteria and mammalian cells.
Genetically modified algae provided the production of four of the seven tested therapeutic proteins in quantities sufficient for commercial use. At the same time, the shape of the synthesized proteins, as well as the ease of their isolation and purification, did not differ from the corresponding parameters provided by traditional synthesis systems.
The production of one gram of complex proteins, such as the drug for the treatment of multiple sclerosis Tysabri (Tysabri) using mammalian cell lines currently costs at least $ 150. (This figure is approximate, as companies prefer not to disclose such information.) Mayfield claims that the use of algae can reduce this figure to almost five cents.
Moreover, the cost of creating a plant for the production of therapeutic protein using mammalian cells can reach 600 million US dollars. This figure is simply monstrous, especially considering that clinical trials conducted after the creation of production, which also require large monetary expenditures, may end in failure. From this point of view, the use of algae also looks like a very attractive prospect.
Unlike bacteria, algae successfully cope with the folding of amino acid chains of complex proteins. In fact, even mammalian cells in some cases incorrectly form protein molecules, which subsequently have to be subjected to additional processing.
In an earlier work, the authors demonstrated the ability of algae to produce human monoclonal antibodies – complex proteins currently obtained with the help of mammalian cells and are the most expensive, but also the most effective existing means for the treatment of cancer. To date, about 100 such antibodies have already been used or are at the stage of clinical trials. However, the cost of a course of treatment with the cheapest drugs of this class is about $ 10,000.
Experts note that, in some cases, it makes no sense to change proven, effectively working drug synthesis systems. At least, systems for the production of simple proteins synthesized by bacteria and yeast, the maintenance of which does not require large financial costs. However, the extreme profitability of algae compared to mammalian cell lines is obvious.
Unlike mammals, algae are not able to glycosylate protein molecules, that is, attach polysaccharide chains to them, without which they do not have the proper effect on the human body. However, Mayfield believes that over time he will be able to solve this issue. To date, he is experimenting with proteins that do not require glycosylation, and in the future he plans to make modifications to the algae genome that will allow them to glycosylate protein molecules with human polysaccharides. Something similar to the experts previously managed to do with yeast.
Mayfield says he hopes to test algae-synthesized proteins on animals by the end of this year. He also noted that researchers from developing countries such as China and India are extremely interested in the technology offered to them and are looking forward to the results.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: Drug Production Gets Aquatic.
22.03.2010