HypoPlant – Production of hypo-allergenic glycoproteins in plants

Glycoproteins (GPs) are of prime interest in the medical sciences. However, production of GPs by standard methods is still complex and expensive.

Plants have been suggested as potential cost-effective and safe GP-production systems; yet, major differences in the final steps of biosynthetic pathways in mammals and plants lead to different glycosylation patterns, provoking an immune response when treating humans with GPs produced in plants. On the other hand, glycosylation is a pre-requisite for proper protein folding, which in case of diagnostic and therapeutic glycoproteins should ideally not include immu-nogenic residues. Challenge State-of-the-art approaches utilize glycosylation mutants or overexpression of the desired protein product (intending to override the cellular glycosylation machinery), although such mutants either show impaired yield or loss of vitality in com-parison to wild-type plants. Also, glycan components rarely terminate in mannose residues, which is essential for uptake via mannose receptors in patients with lysosomal storage diseases. This invention provides a new tool to generate GPs with hypo-allergenic properties in a cost-effective way: In con-trast to current methods, the new technique enables effec-tive production of heterologous GPs by vital plants without impair¬¬ments. The technology is based on genetic modifica-tion of the plant glycosylation pathway. The technology is applicable to solanaceous and other plant species of agronomic interest. Suppression of a specific enzyme results in a general reduction of cross-reactive carbohydrate determinants (CCD) in all tissues, leading to GPs that are better taken up and tolerated by humans.

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