Plant-based biopharmaceutical engineering

Abstract

Plants can be engineered to recombinantly produce high-quality proteins such as therapeutic proteins and vaccines, also known as molecular farming. Molecular farming can be established in various settings with minimal cold-chain requirements and could thus ensure rapid and global-scale deployment of biopharmaceuticals, promoting equitable access to pharmaceuticals. State of the art plant-based engineering relies on rationally assembled genetic circuits, engineered to enable the high-throughput and rapid expression of multimeric proteins with complex post-translational modifications. In this Review, we discuss the design of expression hosts and vectors, including Nicotiana benthamiana , viral elements and transient expression vectors, for the production of biopharmaceuticals in plants. We examine engineering of post-translational modifications and highlight the plant-based expression of monoclonal antibodies and nanoparticles, such as virus-like particles and protein bodies. Techno-economic analyses suggest a cost advantage of molecular farming compared with mammalian cell-based protein production systems. However, regulatory challenges remain to be addressed to enable the widespread translation of plant-based biopharmaceuticals.

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans

“…Notably, the expression might be increased even further by the use of N. benthamiana -optimized expression constructs, and the addition of gene silencing inhibitors, like p19. A possible downside of extreme expression levels could be underglycosylation of target proteins, as observed for high IgG production using the magnICON ® system [ 40 ]. Indeed, a surprising observation in this study was the large variation in GS occupancies.…”

Production of biologically active human basic Fibroblast Growth Factor (hFGFb) usingNicotiana tabacumtransplastomic plants

“…At present, there are successful developments of plant-produced recombinant proteins that have reached the market. Noteworthy examples include avidin (Merck, Germany), as well as the enzymes glucocerebrosidase and pegunigalsidase alfa (Protalix Biopharmaceuticals, Israel), among others, as comprehensively reviewed (Eidenberger et al 2023).…”

A genome‐edited N. benthamiana line for industrial‐scale production of recombinant glycoproteins with targeted N‐glycosylation

“…Plants have been used for the expression of recombinant proteins for about three decades, prompting several interesting market products. [ 1 ] In particular, the development of transient expression tools that allow for the rapid production of complex proteins within days of delivery of the DNA construct to plant leaves has significantly advanced the system. [ 2 ] Nicotiana benthamiana plants are highly suited for transient expression and, as previously demonstrated, can produce monoclonal antibodies in multimeric formats.…”