Sunday, May 17, 2009

Is Tobacco the Next Anti-HIV Weapon?

Thank You Eric Bland, Discovery News

The tobacco plant could soon redeem itself in the eyes of public health experts, say scientists who are producing huge amounts of a powerful but prohibitively expensive HIV drug inside modified tobacco leaves.

"This is very significant news," said Polly Harrison, Director of the Alliance for Microbicide Development, who was not involved with the research.

"So often it's difficult to make enough of a promising drug to even do laboratory studies, but here production is at a level that allows them to literally make tons of the drug," said Harrison.

Scientists have known for years that the drug, known as griffithsin, protects some people from HIV infection by stopping the virus from colonizing the vaginal lining.

What has prevented griffithsin from becoming a standard HIV preventive measure is the cost of producing it.

The only known naturally occurring source of griffithsin is a red algae found off the coast of New Zealand, which grows in amounts too small to be effectively harvested.

Scientists can produce larger amounts of griffithsin by genetically engineering E. coli bacteria to produce the drug, but maintaining the necessarily high temperatures, supplying the raw materials, and harvesting the drug is expensive.

Now scientists have turned to a virus, the tobacco mosaic virus (TMV), that commonly infects tobacco plants.

TMV is rod-shaped, about 18 nanometers wide by 200 to 300 nanometers long. Once the virus enters a plant cell, it hijacks the cell's molecular machinery. Usually the hijacked plant cells are reprogrammed to produce more virus.

The scientists first mail-ordered a synthetic version of the red algae gene that produces griffithsin. They then injected that gene into the TMV, mixed it with water, and sprayed the virus over a greenhouse field of eight-inch-tall Nicotiana benthamiana, a close cousin of commercial tobacco plants that is especially susceptible to TMV.
After a few days the leaves of infected plants began to wilt. The scientists harvested the plants by hand and processed them to extract the griffithsin.

The research is published in this week's edition of the Proceedings of the National Academy of Sciences

The most effective way griffithsin can prevent HIV infection is in a vaginal cream applied before sex, said Kenneth Palmer, a researcher at Owensboro Cancer Research Program who was the corresponding author on the study.

A cigarette containing griffithsin hasn't been discounted either, said Palmer.

Tobacco-derived griffithsin in a gel has already been tested in both mice and in the cells of women who have had their cervix removed. In both cases the griffithsin stopped all HIV transmission without any toxic side effects and without any sign of inflammation or irritation.

The researchers hope to begin phase one FDA clinical trials of the microbicide gel within a year.

A next-generation Human Papilloma Virus (HPV) vaccine, also produced inside Nicotiana benthamiana, is already scheduled for clinical trials later this year.


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