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Old 01-08-2009, 10:36 AM   #1
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Default Transgenic Tobacco Plants

Is this a double edged sword, a trojan horse into GM?

HIV Microbicides from Transgenic Tobacco Plants
31 July 2009

When you think of tobacco, what's the first thing that comes to mind? You won't think of health benefits, of course. Tobacco use has been associated with numerous diseases, including certain forms of cancer. But the plant could soon redeem itself in the eyes of health experts. Two teams of scientists have recently used tobacco to make large amount of proteins that could prevent the transmission of the human immunodeficiency virus (HIV), bringing the prospect of commercial, protein-based microbicides a step closer to reality.

Despite more than two decades of intense research efforts, scientists are yet to come up with an effective vaccine against HIV. With the absence of an effective HIV vaccine in the horizon, scientists are turning their attention to other prevention methods, particularly the use of topical microbicides.

Researchers from the University of Louisville in Kentucky have developed transgenic tobacco plants accumulating high levels of griffithsin (GRFT), a protein that has been shown to be effective against HIV even at picomolar concentrations. The protein, originally produced by a red algae, kills HIV by binding to the envelope glycoprotein.

In a paper published by PNAS, Kenneth Palmer and colleagues reported that they were able to produce 60 grams of pure GRFT from tobacco plants grown in a single 5,000 square-foot enclosed greenhouse.

The recombinant griffithsin was found to be effective against HIV strains A, B, C. Strains A and C are predominant in Sub-Saharan Africa and the Indian subcontinent, regions where microbicides are urgently needed. GFRT also presents an advantage over other microbicides, for instance lectins, since it does not stimulate lymphocyte proliferation. Furthermore, the protein has a high melting temperature, which may provide many practical advantages for shipping and storage of in resource-poor areas.

Another team of researchers from the University of London, led by Julian Ma, has also been successful in developing tobacco plants that produce potent HIV microbicides.

The researchers combined two known protein microbicides, b12 monoclonal antibody and cyanovirin-N, into a single molecule and produced it in planta. They showed that that the fusion protein has greater anti-HIV potency compared to its individual components.

Cyanovirin-N originates from a blue-green algae. "A major effort was made to produce the protein in E. coli, but technical difficulties overcame that work," explained Julian Ma. "Monoclonal antibodies, on the other hand, are made in fermentation tanks by growing recombinant Chinese Hamster Ovary cells. This is an efficient means of making antibodies, but no-one yet has succeeded in making the microbicide described here in a system other than plants."

Clinical trials of non-protein microbicides against HIV have been dismal. Recently, a late-stage trial of a microbicide gel, involving more than 1000 women in India, South Africa and Uganda, was halted after the gel was found ineffective in preventing HIV transmission. Researchers hope that protein-based microbicides will perform better.

"The first microbicide trial investigated microbicide candidates that were simple and straightforward to get to clinical trial," said Julian Ma. "They did not have particularly strong anti-HIV activity. The next generation of microbicides are much better candidates, they target HIV better and they have much higher HIV neutralization capacity. Some of these, like the ones we are working on, are proteins, which are difficult to manufacture in large quantities and cheaply, which is why it has taken time to reach trials."


Last edited by cruise4; 01-08-2009 at 10:36 AM.
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