Agriculture has been an integral part of human existence for over ten thousand years. A 2021 perspective article published in Science, the journal of the American Association for the Advancement of Science, explores an alternative way of utilizing plants. The authors, Drs. Hugues Fausther-Bovendo and Gary Kobinger at Faculty of Medicine, Universite Laval, Quebec and Galveston National Laboratory, Texas, respectively, review the advantages and challenges of molecular farming.
Molecular farming, or the idea of using plants for producing medicines and vaccines, dates back to 1986. But it wasn’t until 2012 and the approval of the first, and currently only, plant-derived therapeutic protein for treating Gaucher disease, a genetic disorder characterized by fat cell accumulations in the spleen, liver, and bone marrow, that it generated much attention. The successful completion of Phase III clinical trials of a plant-produced flu vaccine in 2019 and the start of Phase III trials for a plant-made COVID-19 vaccine in March 2021 further propelled the vision of plant-synthesized pharmaceuticals for humans, including edible drugs.
Among the main advantages of molecular farming are affordability, ease of accessibility and scalability, and reduced risk of contamination. Unlike the currently dominant way of producing therapeutics in bacteria or eukaryotic systems, such as chicken eggs or mammalian or insect cell cultures, plants only need light, water, and soil to grow. And procuring greenhouses, if necessary, is far cheaper than creating the sterile environments required of drug-making facilities. Furthermore, production can easily be scaled by increasing or reducing the number of plants grown. Also, zoonotic pathogens, disease-causing germs that are a common threat in traditional production systems, cannot infect plants and thus contaminate molecular farming products.
Technological progress, more particularly the advancement of gene-editing tools, has further amplified molecular farming's potential benefits. Scientists have registered yields of over 1 mg/g of fresh plant weight. In comparison, the typical yields for Chinese hamster ovary cell cultures range from 5 to 20 g/liter. The authors also write about increased production speed, with a harvest made possible within days in some instances. The faster production could be particularly beneficial for personalized medicine, which requires customization of treatment to the individual patients’ needs. It could also help against new pathogens or emerging strains with plant-based vaccines readily available within weeks.
Regarding vaccines, plant-synthesized proteins surpass those obtained via bacterial, mammalian, or insect systems in several ways. Plants’ posttranslational modification capabilities render plant-derived proteins more immunogenic than their mammalian counterparts. That is, plant-made vaccines won’t require an adjuvant, an additive that further stimulates the recipient’s immune system, which is present in the majority of traditional vaccines.
While the higher immunogenicity of plant-derived proteins could contribute to simpler and more affordable vaccine formulations, it could also trigger allergic reactions toward plant components. Thus, scientists must ensure that plant-based vaccines won’t cause any hypersensitivity against the plants used for production, especially when it comes to popular ones such as rice, cereals, and corn. Another challenge for molecular farming is the rather expensive facilities required for extracting, purifying, and filling plant-derived therapeutics under good manufacturing practice (GMP). The discrepancy between the needed larger doses and the limited manufacturing capacity will pose an additional obstacle. Currently, fewer than 15 GMP facilities operate globally.
The majority of edible, plant-produced pharmaceuticals are in the preclinical stage of development. If successful, however, they could result in a new class of more accessible and sustainable therapeutic products.
