Plants have been increasingly researched as an alternative recombinant protein expression system. Creative Biolabs is capable of offering different plant production systems to obtain high-quality recombinant proteins of interest. There are three broad plant production systems: whole plant, culture of organized plant tissues and plant cell culture. All these three systems are able to produce recombinant proteins with complex glycosylation patterns and post-translational modification (PTM).
Figure: Biopharmaceutical production in plant cells (Nat Biotechnol, 2004)
Using whole plants to produce proteins has advantages that it is easy to reach agricultural-scale production with low capital equipment costs and scalability. But its development time is long and has variations in product yield and quality, moreover, it is difficult to apply good manufacturing practice (GMP) to the early stages of production. Now there are more than 100 plants that can be induced to produce hairy roots in culture. Production of pharmaceuticals by this system is over-production of a pharmaceutical that are most naturally produced by the plant. The expression system of plant cell cultures avoids these problems but retain the advantages. Firstly, plant cells can be cultured in simple, synthetic media with inexpensive cost. Secondly, as higher eukaryotes, they can perform PTMs that occur in human cells and synthesize complex multimeric proteins and glycoproteins such as interleukins and immunoglobulins. Thirdly, plant cells neither harbor human pathogens nor produce endotoxins, so they are intrinsically safe. Finally, cGMP can be applied throughout the production pipeline of plant cells. Taliglucerase alfa is an enzyme with a human compatible glycan profile which is produced by genetically modified carrot plant root cells and has been approved by FDA.
There are various approaches that can be used for cultivation of plant cells, such as derivation of shooty teratomas, hairy roots, suspension cells and immobilized cells. Among which suspension cells are preferred because they are the most amenable to GMP procedures. Up to now, suspension cells have been identified from various plant species including Catharanthus roseus, Taxus cuspidata, Arabidopsis thaliana and crops such as soybean, alfalfa, tobacco, tomato, rice, etc. BY-2, NT-1 and the closely related cultivars are tobacco suspension cells and are frequently chosen as host cell lines. These cells have favorable growth characteristics and their transformation and propagation are simple and well-established. During the design of constructs used to express the recombinant proteins, promoter and lead peptide choice affects the yield. The most widely used promoters include constitutive promoters and inductive promoters. Cauliflower mosaic virus (CaMV) 35S, hybrid (ocs)3mas promoter, hybrid (ocs)3mas promoter, ubiquitin promoters from maizeand A. thaliana3, rice α-amylase RAmy3D promoter induced by sugar deprivation are commonly used. The lead peptides are from plant or non-plant proteins, which have equivalent function. And several human recombinant proteins have been expressed in plant cells using their own endogenous leaders.
Integrated by advanced platforms, Creative Biolabs performs GMP or non-GMP process development to obtain plant cells with improving productivity.
References:
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Stephan Hellwig, et al. Plant cell cultures for the production of recombinant proteins. Nat Biotechnol. 2004 Nov;22(11):1415-22.
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Rigano MM and Walmsley AM. Expression systems and developments in plant-made vaccines. Immunol Cell Biol. 2005 Jun;83(3):271-7.
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