Topical drugs are easy to administer, and are especially attractive for combating HIV infection. However, they are expensive, and previous efforts have focused on producing them under rigorous, small-scale laboratory conditions.
This has hindered the development and practical, widespread use of topical anti-HIV drugs. One that is cheap, can be mass produced, and is (of course) effective is likely to be of huge therapeutic benefit, especially as a means for females to prevent HIV infection.
Kenneth Palmer (Intrucept Biomedicine and University of Louisville, Kentucky) and coworkers have overcome these challenges. They have produced their topical anti-HIV drug on a multi-gram scale from genetically modified plants, and have preliminarily demonstrated its safety and broad efficacy against HIV.
Producing the drug in plants.
The scientists desired to produce their anti-HIV drug in genetically modified plants. The intention was to produce it cheaply, on a large scale, in nonsterile conditions; in other words, a practical production method.
They used Nicotiana benthamiana plants for these purposes. This Australian plant is related to tobacco, and is commonly used in plant research.
They infected this plant with the tobacco mosaic virus, itself genetically modified to synthesize griffithsin, the scientists' anti-HIV protein drug. Thus, the infected plants would synthesize the drug, effectively serving as a cheap drug factory.
Nine thousand three hundred plants in a 5000 square foot greenhouse were infected. The plants were readily processed for drug extraction after 12 days, in only a few steps.
The protein drug comprised up to one gram per kilogram of total plant material, much greater than any other anti-HIV protein drugs produced in plants or bacteria. After processing, the drug was greater than 99.8% pure.
Anti-HIV activity.
Cheaply and easily producing large quantities of the drug in plants is not enough. The drug must also effectively target HIV.
The scientists' initial studies investigated drug efficacy under model laboratory conditions. They found that it inhibited HIV entry into immune cells, and was effective against HIV strains A, B, and C, although the level of efficacy depended on the specific subtype of HIV.
This suggests that the scientists' drug is effective against every strain of HIV. It is also far more potent than other drugs currently available, and does not cause inflammation.
Overall evaluation.
Griffithsin is stable topically for at least one day. Additionally, it is resistant to acidic pH, carbon-based solvents, freeze-thaw cycling, freeze-drying, and electron-donating ("reducing") chemicals.
This means that the scientists' anti-HIV drug is amenable to a wide range of shipping and storage conditions. This is especially important for financially strained nations.
In combination with its low cost, easy large-scale production, and clear preliminary efficacy and safety, this drug is an obvious candidate for large-scale clinical anti-HIV trials. It shows a great deal of promise, despite the widely publicized recent failures of other anti-HIV drugs.
for more information:
O'Keefe, B. R.; Vojdani, F.; Buffa, V.; Shattock, R. J.;
Montefiori, D. C.; Bakke, J.; Mirsalis, J.; d'Andrea, A.-L.;
Hume, S. D.; Bratcher, B.; Saucedo, C. J.; McMahon, J. B.;
Pogue, G. P.; Palmer, K. E.
Scaleable manufacture of HIV-1 entry inhibitor griffithsin and
validation of its safety and efficacy as a topical
microbicide component.
Proc. Natl. Acad. Sci. USA 2009, 106, 6099-6104.