ArticlePloS one2013
Generation of biologically active multi-sialylated recombinant human EPOFc in plants.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
- Review
- Protein engineering strategies to optimise recombinant product synthesis and accumulation in Nicotiana benthamiana.Plant biotechnology journal · 2026Review
- Posttranslational modifications of heterologous proteins expressed in Nicotiana benthamiana.Plant biotechnology journal · 2026Review
- An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction.Plant cell reports · 2025Article
- Advances and challenges in plant N-glycoengineering: when fucosylation matters.Frontiers in plant science · 2025Review
- Plant-made pharmaceuticals.Plant biotechnology (Tokyo, Japan) · 2024Article
- Product safety aspects of plant molecular farming.Frontiers in bioengineering and biotechnology · 2023Review
- Plant-based biopharmaceutical engineering.Nature reviews bioengineering · 2023Review
- Improving Protein Quantity and Quality-The Next Level of Plant Molecular Farming.International journal of molecular sciences · 2022Review
- SARS-CoV-2 spike binding to ACE2 is stronger and longer ranged due to glycan interaction.Biophysical journal · 2022Article
- Targeted genome editing of plants and plant cells for biomanufacturing.Transgenic research · 2021Review
- Generation of enzymatically competent SARS-CoV-2 decoy receptor ACE2-Fc in glycoengineered Nicotiana benthamiana.Biotechnology journal · 2021Article
- Glyco-Engineering of Plant-Based Expression Systems.Advances in biochemical engineering/biotechnology · 2021Article
- Reteplase Fc-fusions produced in N. benthamiana are able to dissolve blood clots ex vivo.PloS one · 2021Article
- Impact of SpecificFrontiers in plant science · 2021Article
- The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology.Frontiers in plant science · 2021Article
- Lewis A Glycans Are Present on Proteins Involved in Cell Wall Biosynthesis and Appear Evolutionarily Conserved Among NaturalFrontiers in plant science · 2021Article
- Glycoengineering tobacco plants to stably express recombinant human erythropoietin with different N-glycan profiles.International journal of biological macromolecules · 2020Article
- Synthetic Glycobiology: Parts, Systems, and Applications.ACS synthetic biology · 2020Review
- BGAL1 depletion boosts the level of β-galactosylation of N- and O-glycans in N. benthamiana.Plant biotechnology journal · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperglycosylated proteins are more stable, show increased serum half-life and less sensitivity to proteolysis compared to non-sialylated forms. This applies particularly to recombinant human erythropoietin (rhEPO). Recent progress in N-glycoengineering of non-mammalian expression hosts resulted in in vivo protein sialylation at great homogeneity. However the synthesis of multi-sialylated N-glycans is so far restricted to mammalian cells. Here we used a plant based expression system to accomplish multi-antennary protein sialylation. A human erythropoietin fusion protein (EPOFc) was transiently expressed in Nicotiana benthamiana ΔXTFT, a glycosylation mutant that lacks plant specific N-glycan residues. cDNA of the hormone was co-delivered into plants with the necessary genes for (i) branching (ii) β1,4-galactosylation as well as for the (iii) synthesis, transport and transfer of sialic acid. This resulted in the production of recombinant EPOFc carrying bi- tri- and tetra-sialylated complex N-glycans. The formation of this highly complex oligosaccharide structure required the coordinated expression of 11 human proteins acting in different subcellular compartments at different stages of the glycosylation pathway. In vitro receptor binding assays demonstrate the generation of biologically active molecules. We demonstrate the in planta synthesis of one of the most complex mammalian glycoforms pointing to an outstanding high degree of tolerance to changes in the glycosylation pathway in plants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.