1-Proteins: GE algae produce human antibodies
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TITLE: Growing Human Antibodies in Algae is an Inexpensive and Fast Route
to Large-Scale Production, Say Scientists at The Scripps Research
SOURCE: The Scripps Research Institute, USA
DATE: Jan 15, 2003
------------------ archive: http://www.gene.ch/genet.html ------------------
Growing Human Antibodies in Algae is an Inexpensive and Fast Route to
Large-Scale Production, Say Scientists at The Scripps Research Institute
La Jolla, CA. January 15, 2003 - 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
"This is a fast, new, effective way to make human therapeutic proteins,"
says TSRI Associate Professor Stephen P. Mayfield, Ph.D., who conducted
the research with Research Associate Scott E. Franklin, Ph.D., and TSRI
President Richard A. Lerner, M.D.
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
"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 which can be produced with
current technologies, has 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.
For more information contact:
Jason Bardi 10550 North Torrey Pines Road La Jolla, California 92037