Prospects to produce cancer medicine from algae

(biococv) - Biologists have designed algae to create complex anti-cancer drugs. Biologists at UC San Diego University have succeeded in engineering genetically modified algae to produce a complex and expensive drug used to treat cancer.

This achievement is detailed in an article in the journal Proceedings of the National Academy of Sciences , opening the door to creating such proteins and other 'designer' proteins in greater numbers and dates. the cheaper the protein is made from mammalian cells.

"Because we can make the exact same drug in algae, we have the opportunity to reduce prices significantly , " said Stephen Mayfield, a biology professor at UC San Diego and director of China. Mind algae biotechnology (Algae Biotechnology or SD-CAB) statement.

This is a group of research organizations that are also working to develop new biofuels from algae.

Their method can even be used to create complex designed pills that cannot be produced by any other system, pills that can be used to treat cancer or other drugs. Other human illnesses in new ways.

"You cannot make these drugs in bacteria because bacteria are unable to fold proteins into three-dimensional shapes and complexes," Mayfield said. "And you can't make these proteins in mammalian cells because toxins can kill them."

This success is the culmination of 7 years of research in Mayfield's laboratory to prove that Chlamydomonas reinhardtii algae, a green algae, is widely used in biological laboratories as a tissue organism. Genetic images can produce a variety of human proteins in larger and cheaper quantities than bacteria or mammalian cells.

Mayfield and his colleagues achieved their first breakthrough five years before they proved they could create a mammalian amyloid protein in algae. In the following year, they succeeded in using algae to produce a human antibody protein. In 2010, they demonstrated that more complex proteins - human therapeutic drugs, such as endothelial growth factor, or VEGF, were used to treat patients suffering from emphysema - can be produced in algae.

Then, in May this year, Mayfield's team worked with another research team, led by Joseph Vinetz from UC San Diego Medical School, designed algae to produce a more complex protein - A new, preliminary experimental vaccine shows that it can protect billions of people from malaria, one of the most common diseases in the world.

"The development of malaria vaccines shows us that algae can produce really complex structural proteins, which contain a lot of disulfide bonds, which fold into three-dimensional structures. " Mr. Mayfield said. "Antibodies are the first complex proteins we make. However, the malaria vaccine is complex, with disunphide links quite unusual. So once we did that, we believe we can do anything in algae ".

In their latest development, the scientists transformed the algae gene to produce three-dimensional, complex proteins with two "domains" - one of which contained an antibody, possibly a residence and attack. To a cancer cell and another domain that contains a toxin, this toxin kills cancer cells outside the border. So the current "fusion protein" is produced by pharmaceutical companies in a complex process of two steps by developing the first antibody domain in a Chinese hamster cell, or CHO. Antibodies are refined, then attached to a toxin outside the cell. After that, the final protein is re-purified.

Domain structure can be defined as parts, areas in a protein molecule folded in space like a complete small protein molecule and often a place to perform functional, functional assembly of protein molecules in its functional activity. In many protein domains associated with specific combination functions and in many enzymes made up of domains, the re-operation center is located on the border of two or more domains. The formation of domains in protein molecules creates the ability to interact flexibly between macromolecules, the ability to maneuver, move accordingly among parts in the process of implementing biological functions. In different origin proteins, but with similar functions, domains have relatively similar structures.

"We have a double advantage over that process," Mayfield said. "First, we do this as a single protein with antibodies and toxic domains that merge together in a single gene, so we only have to refine it a second time. We do this in algae instead of in CHO cells, we have the advantage of much more cost in producing proteins ".

The fusion protein that lab researchers produced from algae is similar to one developed by pharmaceutical companies with a proposed cost of more than $ 100,000. The researchers said the same protein could be produced in algae at a fraction of the price. And UCSD researchers - Miller Tran, Christina Van, Dan Barrera and Jack Bui, at UC San Diego Medical School - confirm that this compound works like more expensive treatments: it has resided on. Cancer cells and inhibit tumor growth in laboratory mice.

Mayfield said such a fusion protein might not have been produced in a mammalian cell, because the toxins would kill the animal. But because proteins are produced in the chloroplasts of algae - where photosynthesis takes place - these proteins did not kill algae.

"Protein is isolated inside chloroplasts," Mayfield said. "And chloroplasts have different proteins than the rest of the cells, and these proteins are not affected by toxins. If the proteins we create are out of the chloroplast, it may have killed the cells, so it's great to think that no molecule has escaped from the chloroplasts, there are thousands of copies of that protein inside. the chloroplasts and they did not escape. '

Mayfield said that producing this special fusion protein is quite simple because it involves mixing two domains - one to identify and bind to cancer cells and the other to kill them. But in the future, he thinks that methods like this could be used to design algae to produce more complex proteins with more domains.

"Can we combine four or five properties and produce a design protein in algae with a multi-function that doesn't exist in nature? I think we can?" he added. "Suppose I want some protein receptors with a variety of activated proteins so that I can stimulate bone production or neuronal production? At some point you can start thinking about the types. The drug in the same way we think about assembling a computer, combining different modules with specific purposes, we can produce a protein with a domain that targets the type of cell you want to impact, and another domain determines what you want the cell to do. "

The research project is supported by grants from the National Science Foundation and the Skaggs Family Foundation.