TSRI Scientists Succeed in Growing Human Antibodies in Algae

By Jason Socrates Bardi

A group of scientists at The Scripps Research Institute (TSRI) have used algae to express an antibody that targets herpes virus, describing the work in an upcoming issue of the journal Proceedings of the National Academy of Sciences.

This antibody could potentially be an ingredient in an anti-herpes topical cream or other anti- herpes treatments, but more importantly the algae expression technology that the TSRI team used could facilitate production of any number of human antibodies and other proteins on a massive scale.

"This is a fast, new, effective way to make human therapeutic proteins," says TSRI Associate Professor Stephen P. Mayfield, who conducted the research with Research Associate Scott E. Franklin and TSRI President Richard A. Lerner.

Significantly, the researchers were able to produce the antibody at a much lower cost than has been achieved in the past. In fact, they say they can now make antibodies, soluble receptors, and other proteins so much more cheaply that an entire new class of therapeutics may become accessible.

"You can't make [a drug] if the time and expense is such that you have to sell that drug for hundreds of thousands of dollars," says Mayfield. "This has to be the way we make drugs in the future."

From Pond Scum to Pharmacy Shelf

Also called immunoglobulins, antibodies are proteins produced by immune cells that are designed to recognize a wide range of foreign pathogens. After a bacterium, virus, or other pathogen enters the bloodstream, antibodies target antigens—proteins, carbohydrate molecules, and other pieces of the pathogen—specific to that foreign invader. These antibodies then alert the immune system to the presence of the invaders and attract lethal "effector" immune cells to the site of infection.

Antibodies can also be useful as therapeutics for a number of human diseases ranging from rheumatoid arthritis to leukemia. Likewise, there are many other human proteins that could potentially be used as drugs.

In fact, there may be over 200 proteins that could potentially be new anti-cancer, anti- inflammatory, anti-arthritis compounds, says Mayfield. As an example, an anti-IgE antibody, termed Omalizumab, has already shown great efficacy in human clinical trials for the treatment of allergic rhinitis and asthma. Unfortunately, the costs of producing the antibody, coupled with the relatively small amounts that can be produced with current technologies, have severely limited its availability.

In cases where scientists want to make an abundance of proteins, they often turn to the simplest expression system—bacteria. However, this does not work for large, complicated proteins like antibodies because bacteria do not have the machinery to assemble them into the correct structure. So large proteins are usually produced through an expensive and complicated process involving the fermentation of mammalian cells.

Algae may offer a cheaper and easier way to produce the proteins. Since algae grow naturally and use carbon dioxide from the air as a carbon source and sunlight as an energy source, whole ponds—tens of thousands of liters—of the algae can be grown once they are modified to produce the protein of interest.

"The scale on which you can grow these algae is enormous," notes Franklin.

Modifying the algae to produce proteins entails inserting a gene into the genome of the chloroplast, the organelles within the alga cell that converts sunlight and carbon dioxide into plant matter. The algae then express and assemble the antibodies within the chloroplasts, which can later be purified, intact.

Now that the researchers have established the fundamental technology, they are looking at applying it to any number of proteins and receptors.

"We think we can now put in pretty much any gene that we want and have it express," says Mayfield.

The article, "Expression and assembly of a fully active antibody in algae," authored by Stephen P. Mayfield, Scott E. Franklin, and Richard A. Lerner, is available online at: http://www.pnas.org/cgi/content/abst ract/0237108100v1 and will be published in the journal Proceedings of the National Academy of Sciences on January 21, 2003.

This work was supported by funds from Sea Grant, the National Institutes of Health, and Syngenta Corporation.





Antibodies (top) expressed in Algae (middle) can be grown for commercial production in large scale ponds, like these in Kailua-Kona, Hawaii (bottom). (Picture of intact human "b12" antibody courtesy Robyn Stanfield and Ian Wilson. Image of Chlamydomonas (algae) Copyright Charles J. O'Kelly and Tim Littlejohn. Kailua-Kona picture courtesy of Cyanotech.)