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.
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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.)
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