Plants as factories for production of biopharmaceutical and bioindustrial proteins: lessons from cell biologyThis review is one of a selection of papers published in the Special Issue on Plant Cell Biology.

Abstract

Transgenic plants, seeds, and cultured plant cells are potentially one of the most economical systems for largescale production of recombinant proteins for industrial and pharmaceutical uses. Biochemical, technical, and economic concerns with current production systems have generated enormous interest in developing plants as alternative production systems. However, various challenges must be met before plant systems can fully emerge as suitable, viable alternatives to current animal-based systems for large-scale production of biopharmaceuticals and other products. Aside from regulatory issues and developing efficient methods for downstream processing of recombinant proteins, there are at least two areas of challenge: (1) Can we engineer plant cells to accumulate recombinant proteins to sufficient levels? (2) Can we engineer plant cells to post-translationally modify recombinant proteins so that they are structurally and functionally similar to the native proteins? Attempts to improve the accumulation of a recombinant protein in plant cells require an appreciation of the processes of gene transcription, mRNA stability, processing, and export, and translation initiation and efficiency. Likewise, many post-translational factors must be considered, including protein stability, protein function and activity, and protein targeting. Moreover, we need to understand how the various processes leading from the gene to the functional protein are interdependent and functionally linked. Manipulation of the post-translational processing machinery of plant cells, especially that for N-linked glycosylation and glycan processing, is a challenging and exciting area. The functions of N-glycan heterogeneity and microheterogeneity, especially with respect to protein function, stability, and transport, are poorly understood and this represents an important area of cell biology.Résumé : Les plantes, les graines et les cellules végétales cultivées transgéniques constituent potentiellement un des systè-mes les plus économiques pour la production à grande échelle de protéines recombinantes, pour des usages industriels et pharmaceutiques. Les contraintes biochimiques, techniques et économiques des systèmes de production actuels ont généré un énorme intérêt pour le développement des plantes comme systèmes de production alternatif. Cependant, divers défis doivent être rencontrés, avant que des systèmes végétaux puissent émerger comme alternatives adaptées et viables aux systèmes actuels basés sur les animaux, pour la production à grande échelle de produits biopharmaceutiques et autres. En plus des problèmes de réglementations et du développement de méthodes efficaces pour le traitement en aval des protéines recombinantes, on trouve au moins deux groupes de défis : (1) Pouvons-nous programmer les cellules végétales de manière à accumuler les protéines recombinantes en teneurs suffisamment élevées? (2) Pouvons-nous programmer les cellules végé-tales pour la modification post-traductionnelle des protéines recombinantes de manière à ce qu'elles s...

Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives

“…With the advances in plant biotechnology, transgenic plants have also been explored as sources for recombinant lysosomal enzymes due to the lower cost, less contamination risk with human pathogens, and large-scale supply [199]. The major drawback of this system is that post-translational modifications in the Golgi add residues that are potentially immunogenic to humans [200].…”

“…The major drawback of this system is that post-translational modifications in the Golgi add residues that are potentially immunogenic to humans [200]. Hence, strategies to reduce plant-specific maturation have been attempted [199]. One approach tried to retain proteins in the ER, preventing their transit to Golgi compartments, attempted for production of α-L-iduronidase in maize seeds [201].…”

Plant volatiles: Production, function and pharmacology

“…However, various challenges must be met before plant systems can fully emerge as suitable, viable alternatives to current animal-based systems for the large-scale production of agrochemicals and other products. 106 Production and genetic manipulation of natural products via plant cell suspension culture is renewable, environmentally friendly, and, from a processing standpoint, amenable to strict control, a considerable advantage regarding Food & Drug Administration (FDA) manufacturing standards. 107,108 Although considerable improvement have been made in terms of yields of secondary metabolite production, also for compounds that accumulate only at low levels, relatively little progress has been made in understanding and controlling the instability of some secondary metabolite production patterns.…”

Cloning, Transformation and Expression of Proinsulin Gene in Tomato (Lycopersicum esculentum Mill.)

“…There is greater public acceptance for plants derived medicines compared to other platforms like Chinese hamster ovary (CHO), yeast, etc. making plants favorable hosts as expression platforms for providing a recombinant biopharmaceuticals (14-16). After production of transgenic tobacco and sunflower in 1986, progress was made in the molecular farming era.…”