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Freeze-dried lettuce leaves are a surprising new source for shelf-stable drugs, report researchers.
Biopharmaceuticals, or drugs that are based on whole proteins, are expensive to make and require refrigeration to store. Insulin, for example, is unaffordable and inaccessible to most of the global population.
In a study published in the journal Biomaterials, the researchers confirm the viability of their method for FDA approval and human use, producing an effective drug that promotes tolerance to clotting factors, which could be taken by hemophilia patients, using freeze-dried lettuce leaves.
The study builds on previous work by Daniell’s group demonstrating an ability to use genetically modified plants to introduce a protein into the body that would teach the immune system to tolerate clotting factors used to treat hemophilia.
Normally, 20 to 30 percent of people who get infusions of clotting factor develop antibodies against them that interfere with treatment. The earlier study, published in the journal Blood, successfully stopped and even reversed the production of these clotting factor inhibitors by feeding the plant-based drug to mice with hemophilia A.
NOT TOBACCO: That study used a tobacco plant platform to “grow” the drug. To take this approach into humans, however, Daniell’s team knew they needed to use a different plant species.
They launched work with lettuce, which required using a completely different genetic vector to introduce the therapeutic gene into the plant cell’s DNA, as the tobacco construct would not work in a different species.
After identifying a compatible vector, they used a similar protocol to their previous work, bombarding lettuce leaves with a fusion of the therapeutic protein, coagulation factor IX, or FIX, with cholera toxin B subunit, which allows the protein to reach the immune system. They then evaluated the resulting plants for those that took it up and then grew those plants to maturity.
The next step was to ensure that the drug would be shelf stable. To do that, they freeze dried the plant material, ground it, and analyzed the resulting fine powder for expression levels of the fusion protein to determine the appropriate dose and to evaluate its efficacy.
Similar to their previous experiments, Herzog’s lab fed hemophilia B mice with a suspension of plant cell containing clotting factor IX twice a week for eight weeks and then gave them the same clotting factor that human hemophilia patients take to encourage blood clotting. As before, their product was a success: mice given the drug had greatly suppressed inhibitor formation compared to untreated animals, even when various doses of the drug were tested.
