[ Watch the Video: Biology Helping To Engineer Drugs ]
Connie K. Ho for redOrbit.com — Your Universe Online
Pond scum may be undervalued, but a team of scientists recently discovered it could have biological value. Researchers from the University of California, San Diego (UCSD) recently revealed that they have successfully genetically engineered algae that can make a complex, therapeutic drug that is anti-cancer.
The researchers believe that the results of the experiment allow for more “designer” proteins to be made with mammalian cells in larger quantities and at less cost. The team of investigators used a method on the green alga, known as Chlamydomonas reinhardtii, that could develop new ways of treatment on cancer and other human diseases.
“Because we can make the exact same drug in algae, we have the opportunity to drive down the price down dramatically,” explained Stephen Mayfield, a professor of biology at UCSD, in a prepared statement.
In the past, Chlamydomonas reinhardtii has been used as a genetic model organism.
“You can´t make these drugs in bacteria, because bacteria are incapable of folding these proteins into these complex, three-dimensional shapes,” commented Mayfield, who also serves as director of the San Diego Center for Algae Biotechnology (SD-CAB), in the statement. “And you can´t make these proteins in mammalian cells because the toxin would kill them.”
Researchers first discovered that they could use the algae to create a mammalian serum amyloid protein five years ago. The next year, they were able to have the algae make a human antibody protein. In 2010, the scientists were successful in showing how complex proteins like human vascular endothelial growth factor (VEGF), utilized as a human therapeutic drug, could be made in algae. This past May, the researchers in Mayfield´s laboratory collaborated with a team from UCSD´s School of Medicine to engineer algae that could develop a new kind of vaccine that could help the body fight against malaria. This new protein could affect millions around the world who are affected by malaria.
“What the development of the malarial vaccine showed us was that algae could produce proteins that were really complex structures, containing lots of disulfide bonds that would still fold into the correct three-dimensional structures,” continued Mayfield in the statement. “Antibodies were the first sophisticated proteins we made. But the malarial vaccine is complex, with disulfide bonds that are pretty unusual. So once we made that, we were convinced we could make just about anything in algae.”
With the recent findings, the biologists engineered algae to create a complex, three-dimensional protein that has two “domains.” In one domain, there is an antibody that can target and attach to a cancer cell. In the other domain, there is toxin that works to eliminate the cancer cell. Currently, pharmaceutical companies are working on producing these “fusion proteins” in a two-stage progress. They begin by developing the antibody domain in a Chinese hamster cell. Once the antibody is purified, they then chemically attach the toxin to the outside of the cell and the final protein is re-purified. This process to produce the fusion protein costs the companies approximately more than $100,000.
“We have a two-fold advantage over that process,” remarked Mayfield in the statement. “First, we make this as a single protein with the antibody and toxin domains fused together in a single gene, so we only have to purify it one time. And second, because we make this in algae rather than CHO cells, we get an enormous cost advantage on the production of the protein.”
The researchers believe that their production of the fusion proteins from algae is more cost effective. They report that the compounds works similarly to the process used by the pharmaceutical companies, targeting cancer cells and stopping the development of tumors in lab mice. The protein is developed in the algae´s chloroplasts, where photosynthesis takes place, and its ends up not killing the algae.
“The protein was sequestered inside the chloroplast,” noted Mayfield in the statement. “And the chloroplast has different proteins from the rest of the cell, and these are not affected by the toxin. If the protein we made were to leak out of the chloroplast, it would have killed the cell. So it´s amazing to think that not one molecule leaked out of the chloroplasts. There are literally thousands of copies of that protein inside the chloroplasts and not one of them leaked out.”
Moving forward with the study, the researchers plan to work on producing more complex proteins with multiple domains.
“Can we string together four or five domains and produce a designer protein in algae with multiple functions that doesn´t exist in nature? I think we can?” said Mayfield in the statement. “Suppose I want to couple a receptor protein with a series of activator proteins so that I could stimulate bone production or the production of neurons? At some point you can start thinking about medicine the same way we think about assembling a computer, combining different modules with specific purposes. We can produce a protein that has one domain that targets the kind of cell you want to impact, and another domain that specifies what you want the cell to do.”
The findings were recently featured in the early online issue of the Proceedings of the National Academy of Sciences.
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