Glycosylation plant recombinant protein

Table 1. Genetic Alterations Needed To Improve A -Glycosylation Of Recombinant Proteins Produced In CHO cells, Insect Cells And Plants. 

Engineering Glycosylation of Recombinant Proteins Expressed in Plants... 

Genetic addition and supplementation needed to improve plant recombinant protein glycosylation... 

Studies have shown that plants can make biologically active recombinant proteins through both transgenic and transient expression approaches. Although the plant post-translational machinery is similar to that of mammalian cells, there are some notable differences, e.g. differences in glycosylation, particularly the absence of sia-lation, which may impact the activity of certain proteins. The absence of mammalian enzymes may prevent complex maturation processes that are critical for the biological activity of proteins such as insulin. Fortunately these shortcomings affect the activity of only a limited number of proteins. 

There are many high-molecular-weight, polypeptide, elastase inhibitors which have been isolated from animal or plant sources. Most of these, the non-human proteins, would probably induce an immunogenic response and are not suitable for clinical development. However, a subset of these inhibitors, predominantly human in origin, is being explored as a source for clinically-useful elastase inhibitors. Each of the human compounds is found in a specific location, which probably is its primary site for inhibitory action. The physical properties of many of these natural inhibitors have been reported (see Table 2.i)[45-51]. Due to their size and other physical properties, only intravenous or topical formulations of the proteinaceous inhibitors have been considered for clinical use. The pharmacological studies have included natural inhibitors, recombinant variants (i.e. peptides with identical sequences to the natural inhibitors but not necessarily the same glycosylation) and recombinant mutants (peptides with unnatural sequences) [52],... 

Easy transformation and cultivation make plants suitable for production of many recombinant proteins. Plants are capable of carrying out acetylation, phosphorylation and glycosylation as well as other post-translational protein modifications required for the biological activity of many eukaryotic proteins. Numerous heterologous (recombinant) proteins have been produced in plant leaves, frxrits, roots, tubers and seeds, and targeted to different subcellular compartments, such as the cytoplasm, endoplasmic reticuhrm or... 

Recently, plant cells have also been considered to be an alternative host for the production of recombinant proteins since they are able to glycosylate proteins [133, 139]. Of the various systems used for cultivation, such as hairy roots, immobilized cells, and free cell suspensions, the latter is regarded to be most suitable for large-scale applications. Full-size antibodies, antibody fragments, and fusion proteins can be expressed in transgenic-plantcell systems, such as Nicotiana tahacum, pea, wheat, and rice using shake-flask or fermentation cultures [136]. Yet, these systems are still of low commercial importance due to their unadvantageous productivity. 

Yeast is the third expression system used to produce biopharmaceuticals. As mammalian systems, they possess the ability to cany out post-translational modifications of proteins, although the glycosylation pattern usually varies somewhat from the patterns observed on the native protein or on the protein expressed in mammalian cells. Two recombinant proteins expressed in Saccharomyces cerevisiae are now approved for general medical use hepatitis B surface antigen vaccine and the anticoagulant Hirudin . Alternative promising production systems, in particular transgenic animal and plant systems, are still in development but these systems have to prove that they are technically and economically attractive. 

Strasser R, Altmaim F, SteinkeUner H (2014) Controlled glycosylation of plant-produced recombinant proteins. Curr Opin Biotechnol 30 95—1(X)... 

Protein modification by glycosylation is found in all higher eukaryotes and plant proteins contain N-linllinked glycans. Variations between the glycans associated with native proteins and recombinant forms may complicate immunotherapy, whatever the heterologous expression system, and this is not a problem that is specific to recombinant proteins produced in plants. However, it is important to rmderstand the differences between plant and mammalian glycans in order to evalirate their relative importance. 

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