Abstract
Plant-made pharmaceuticals (PMP) have great potential in terms of production costs, scalability, safety, environmental protection, and consumer acceptability. The first PMP were antibodies and antigens produced in stably transformed transgenic plants in the around 90s. Even though the effort using stable transgenic plants is still going on, the mainstream of PMP production has shifted to transient expression in Nicotiana benthamiana. This system involves the expression vectors by Agrobacterium, and its efficiency has been improved by the development of new vector systems and host engineering. The COVID-19 outbreak accelerated this trend through efforts to produce vaccines in plants. Transient expression systems have been improved and diversified by the development of plant virus vectors, which can be classified as full and deconstructed vectors. Full virus vectors spread systemically, allowing for protein production in the entire plant. Compared with conventional agroinfiltration vectors, excellent virus vectors result in higher protein production. Engineering of host plants has included knocking out gene-silencing systems to increase protein production, and the introduction of glycan modification enzymes so that plant-made proteins more resemble animal-made proteins. Hydroponic cultivation systems in plant factories and environmental controls have contributed to efficient protein production in plants. Considering their advantages and small environmental impact, PMP should be more widely adopted for pharmaceuticals' production. However, the initial investment and running costs of plant factories are higher than open filed cultivation. The next objectives are to develop next-generation low-cost plant factories that use renewable energy and recycle materials based on the idea of circular economy.