Plastid Molecular Pharming II. Production of Biopharmaceuticals by Plastid Transformation

Background: Higher plants have been used in medicine throughout human history. Method: While traditional medicinal uses relied on compounds produced naturally by plants, recent advances have enabled the use of plant-based factories to produce diverse agents including pharmaceuticals, antibiotics, and vaccines. The genes responsible for the production of these substances can be either transiently expressed in plants or integrated into their nuclear genome or plastid genome (plastome) by genetic transformation. This review focuses on the application of plastid transformation of higher plants to produce biopharmaceuticals for human applications that are neither antibiotics nor vaccines. Plastid transformation has several advantages over nuclear transformation and represents a minimal risk of transgene contamination to the environment via pollen grains because plastid genes are in most species normally maternally inherited and thus absent from pollen. Other advantages of sitedirected plastid insertion via homologous recombination include strong gene expression due to the plastid genome's high copy number and resistance to silencing, and the ability to achieve multi-gene expression with a single insertion step. Results: Compared to bacterial systems, plant-based bioreactors offer lower production costs, lower risks of human pathogen contamination, and the possibility of exploiting post-translational modification. Conclusion: Consequently, sustainable plant systems based on different species, plastids, and tissues could become an important source of added value in pharmaceutical production.