Eat your greens

Soon parents will have another reason to make their kids eat their greens. Geneticists are engineering plants like lettuce and tobacco to produce vaccines for diseases like malaria, anthrax and E. coli poisoning.

Henry Daniell, a researcher at the University of Central Florida, has been using transgenic plants as protein factories for years. Using a technique called microprojectile bombardment, Daniell coats tiny microparticles of gold with his vectors—short strands of DNA containing the toxin genes—and shoots them at high velocities and under highly pressurized helium at lettuce or tobacco leaves. Leaves are then cut and placed on a plant regeneration medium and after sequencing to confirm the presence of the toxin genes, the transgenic plants are selected and grown.

By inserting the genes for toxins of common diseases into the chloroplast genome, Daniell has engineered plants to function as bioreactors, pumping out loads of protective proteins he can package as vaccines. A vaccine containing a suitable dose of toxin, for say, E. coli poisoning, would stimulate the immune system to produce antibodies against it and grant the patient immunity.

In 2005, Daniell created an anthrax vaccine that protected 100% of immunized mice from anthrax toxin, for 300 days. He theorized that in humans this would confer immunity for around 50 years. He also isolated 150 milligrams of the protective protein from each plant, meaning a scale-up would produce an astonishing 360 million doses of vaccine from 1 acre of land. As compared to mammalian cell culture systems, genetically-modified plants would be capable of producing engineered proteins in much larger quantities.

Combating diseases in impoverished nations is one of the clear implications of these plant-derived vaccines. One can imagine a scenario where a country like Bangladesh could plant, harvest and purify cholera vaccine-producing plants on-site. Daniell is currently working on a dual-purpose vaccine for cholera and malaria.

Proponents point out that engineered proteins produced in plants are free of bacterial contaminants and human pathogens, a considerable problem with mammalian cell cultures. However, large-scale protein purification methods are costly and production methods would need to be developed for clinical applications—clinical-grade pharmaceutical production requires fully-characterized and contaminant-free materials.

A study published today in the Proceedings of the National Academy of Sciences (PNAS) used tobacco leaves to make antibodies to the West Nile virus. Arizona State University researchers showed the antibodies worked just as well as those derived from mammalian cell culture, protecting mice from the virus even days after infection.

Harnessing plant cells or bacteria as biofactories for protein production—for vaccines or biofuels—is an encouraging ambition of biomedical research. The promise of engineering organisms to synthesize exactly what we need, or perform exactly what we want, is the core of synthetic biology.