Engineering of complex protein sialylation in plants
Open accessAbstract
Significance: Sialic acid (Sia) residues are essential monosaccharides in mammals and confer multiple biological functions. Their precise generation is important for both structure–function studies and biotechnological applications. We describe a unique technology that enables the controlled generation of protein sialylation in Nicotiana benthamiana . The plant engineering approach relies on a combination of endogenous glycan deconstruction and the introduction of human sialylation capabilities. An arrangement of transgenic and transient expression modules resulted in the targeted synthesis of Sia structures in three different linkage types, reaching a polymerization degree exceeding 40 residues (polySia). Importantly, the obtained functional activities of polySia point to novel biotherapeutic applications. Our results highlight the exceptional flexibility of the plant-based expression platform for engineering complex posttranslational protein modifications.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The tobacco plant Nicotiana benthamiana expression system was genetically modified to carry the human-type sialylation pathway and to generate mono-and disialylated structures with α2,3 and α2,6 linkage.
“The tobacco plant Nicotiana benthamiana expression system was genetically modified to carry the human-type sialylation pathway and to generate mono-and disialylated structures with α2,3 and α2,6 linkage (Kallolimath et al., 2016).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kallolimath et al., 2016
Cites
A Simple and General Method for Transferring Genes into Plants
Horsch, R., Fry, J. E., Hoffmann, N. L., Wallroth, M., Eichholtz, D. A., Rogers, S. G., & Fraley, R. T. (1985) · Science · doi:10.1126/science.227.4691.1229 · Cited by 4,699 · see citing works
A Rapid, Simple Spectrophotometric Method for Simultaneous Detection of Nitrate and Nitrite
Miranda, K. M., Espey, M. G., & Wink, D. A. (2001) · Nitric Oxide · doi:10.1006/niox.2000.0319 · Cited by 3,858 · see citing works
Saffarzadeh, M., Jünemann, C., Queisser, M. A., Lochnit, G., Barreto, G., Galuska, S. P., Lohmeyer, J., & Preissner, K. T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032366 · Cited by 1,343 · see citing works
Self-citationImmortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,053 · see citing works
Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
Qiu, X., Wong, G., Audet, J., Bello, A., Fernando, L., Alimonti, J. B., Fausther‐Bovendo, H., Wei, H., Aviles, J., Hiatt, E., et al. (2014) · Nature · doi:10.1038/nature13777 · Cited by 984 · see citing works
Schnaar, R. L., Gerardy-Schahn, R., & Hildebrandt, H. (2014) · Physiological Reviews · doi:10.1152/physrev.00033.2013 · Cited by 745 · see citing works
Self-citationMultifarious roles of sialic acids in immunity
Varki, A. P., & Gagneux, P. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06517.x · Cited by 603 · see citing works
INHIBITION OF NITRIC OXIDE SYNTHASE AS A POTENTIAL THERAPEUTIC TARGET
Hobbs, A. J., Higgs, A., & Moncada, S. (1999) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.39.1.191 · Cited by 596 · see citing works
Marillonnet, S., Thoeringer, C., Kandzia, R., Klimyuk, V. I., & Gleba, Y. Y. (2005) · Nature Biotechnology · doi:10.1038/nbt1094 · Cited by 529 · see citing works
Strasser, R., Stadlmann, J., Schähs, M., Stiegler, G., Quendler, H., Mach, L., Glössl, J., Weterings, K., Pabst, M., & Steinkellner, H. (2008) · Plant Biotechnology Journal · doi:10.1111/j.1467-7652.2008.00330.x · Cited by 516 · see citing works
Self-citationHumanization of yeast to produce complex terminally sialylated glycoproteins
Hamilton, S. R., Davidson, R. C., Sethuraman, N., Nett, J. H., Jiang, Y., Rios, S., Bobrowicz, P., Stadheim, T. A., Li, H., Choi, B.-K., et al. (2006) · Science · doi:10.1126/science.1130256 · Cited by 511 · see citing works
Enhancement of therapeutic protein in vivo activities through glycoengineering
Elliott, S., Lorenzini, T., Asher, S., Aoki, K., Brankow, D. W., Buck, L., Busse, L. A., Chang, D., Fuller, J., Grant, J. R., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt799 · Cited by 510 · see citing works
Frosch, M., Görgen, I., Boulnois, G. J., Timmis, K. N., & Bitter-Suermann, D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.4.1194 · Cited by 384 · see citing works
Hara, S., Takemori, Y., Yamaguchi, M., Nakamura, M., & Ohkura, Y. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90377-0 · Cited by 317 · see citing works
Engineered CHO cells for production of diverse, homogeneous glycoproteins
Yang (2015) · Nature Biotechnology · doi:10.1038/nbt.3280 · Cited by 254 · see citing works
In Planta Protein Sialylation through Overexpression of the Respective Mammalian Pathway
Castilho, A., Strasser, R., Stadlmann, J., Grass, J., Jeż, J., Gattinger, P., Kunert, R., Quendler, H., Pabst, M., Leonard, R., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088401 · Cited by 230 · see citing works
Self-citationA common glycan structure on immunoglobulin G for enhancement of effector functions
Lin, C., Tsai, M.-H., Li, S., Tsai, T.-I., Chu, K., Liu, Y.-C., Lai, M.-Y., Wu, C.-Y., Tseng, Y.-C., Shivatare, S. S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1513456112 · Cited by 200 · see citing works
Disialic, oligosialic and polysialic acids: distribution, functions and related disease
Sato, C., & Kitajima, K. (2013) · The Journal of Biochemistry · doi:10.1093/jb/mvt057 · Cited by 182 · see citing works
Polysialylation controls dendritic cell trafficking by regulating chemokine recognition
Kiermaier, E., Moussion, C., Veldkamp, C. T., Gerardy‐Schahn, R., de Vries, I., Williams, L. G., Chaffee, G. R., Phillips, A. J., Freiberger, F., Imre, R., et al. (2015) · Science · doi:10.1126/science.aad0512 · Cited by 162 · see citing works
Self-citationA Human STX cDNA Confers Polysialic Acid Expression in Mammalian Cells
Scheidegger, E. P., Sternberg, L. R., Roth, J., & Lowe, J. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.39.22685 · Cited by 155 · see citing works
Polysialic acid: Biosynthesis, novel functions and applications
Colley, K., Kitajima, K., & Sato, C. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2014.976606 · Cited by 148 · see citing works
Castilho, A., Gattinger, P., Grass, J., Jeż, J., Pabst, M., Altmann, F., Gorfer, M., Strasser, R., & Steinkellner, H. (2011) · Glycobiology · doi:10.1093/glycob/cwr009 · Cited by 135 · see citing works
Self-citationProtein Determinants for Specific Polysialylation of the Neural Cell Adhesion Molecule
Nelson, R. W., Bates, P. A., & Rutishauser, U. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17171 · Cited by 132 · see citing works
Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes
Lindhout, T., Iqbal, U., Willis, L. M., Reid, A. N., Li, J., Liu, X., Moreno, M., & Wakarchuk, W. W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019266108 · Cited by 112 · see citing works
In VivoAutopolysialylation and Localization of the Polysialyltransferases PST and STX
Close, B. E., & Colley, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.34586 · Cited by 109 · see citing works
Autocatalytic polysialylation of polysialyltransferase‐1.
Mühlenhoff, M., Eckhardt, M., Bethe, A., Frosch, M., & Gerardy‐Schahn, R. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01086.x · Cited by 106 · see citing works
Self-citationSTRASSER, R., STADLMANN, J., SVOBODA, B., ALTMANN, F., GLÖSSL, J., & MACH, L. (2005) · Biochemical Journal · doi:10.1042/bj20041686 · Cited by 105 · see citing works
Self-citationMolecular Cloning of Siaα2,3Galβ1,4GlcNAc α2,8-Sialyltransferase from Mouse Brain
Yoshida, Y., Kojima, N., Kurosawa, N., Hamamoto, T., & Tsuji, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.24.14628 · Cited by 105 · see citing works
Controlled glycosylation of plant-produced recombinant proteins.
Strasser, R., Altmann, F., & Steinkellner, H. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.06.008 · Cited by 96 · see citing works
Self-citationAnti-inflammatory activity of low molecular weight polysialic acid on human macrophages
Shahraz, A., Kopatz, J., Mathy, R., Kappler, J., Winter, D., Kapoor, S., Schütza, V., Scheper, T. H., Gieselmann, V., & Neumann, H. (2015) · Scientific Reports · doi:10.1038/srep16800 · Cited by 95 · see citing works
N-glycosylation Engineering of Biopharmaceutical Expression Systems
Jacobs, P. P., & Callewaert, N. (2009) · Current Molecular Medicine · doi:10.2174/156652409789105552 · Cited by 92 · see citing works
Expression and glycoengineering of functionally active heteromultimeric IgM in plants
Loos, A., Grünwald‐Gruber, C., Altmann, F., Mehofer, U., Hensel, F., Grandits, M., Oostenbrink, C., Stadlmayr, G., Furtmüller, P. G., & Steinkellner, H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320544111 · Cited by 81 · see citing works
Self-citationConstruction of a Functional CMP-Sialic Acid Biosynthesis Pathway in Arabidopsis
Castilho, A., Pabst, M., Leonard, R., Veit, C., Altmann, F., Mach, L., Glössl, J., Strasser, R., & Steinkellner, H. (2008) · PLANT PHYSIOLOGY · doi:10.1104/pp.108.117572 · Cited by 81 · see citing works
Self-citationHildebrandt, H., Mühlenhoff, M., & Gerardy‐Schahn, R. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-1170-4_6 · Cited by 80 · see citing works
Self-citationGeneration of Biologically Active Multi-Sialylated Recombinant Human EPOFc in Plants
Castilho, A., Neumann, L., Gattinger, P., Strasser, R., Vorauer‐Uhl, K., Sterovsky, T., Altmann, F., & Steinkellner, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054836 · Cited by 80 · see citing works
Self-citationSato, C., Inoue, S., Matsuda, T., & Kitajima, K. (1998) · Analytical Biochemistry · doi:10.1006/abio.1998.2718 · Cited by 79 · see citing works
Ilyushin, D. G., Smirnov, I. V., Belogurov, A. A., Dyachenko, I. A., Zharmukhamedova, T. Y., Novozhilova, T. I., Bychikhin, E. A., Serebryakova, M. V., Kharybin, O. N., Мурашев, А. Н., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211118110 · Cited by 75 · see citing works
Rapid High Yield Production of Different Glycoforms of Ebola Virus Monoclonal Antibody
Castilho, A., Bohorova, N., Grass, J., Bohorov, O., Zeitlin, L., Whaley, K. J., Altmann, F., & Steinkellner, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026040 · Cited by 72 · see citing works
Self-citationNakayama, J., Angata, K., Ong, E., Katsuyama, T., & Fukuda, M. (1998) · Pathology International · doi:10.1111/j.1440-1827.1998.tb03967.x · Cited by 64 · see citing works
Bork, K., Reutter, W. G., Weidemann, W., & Horstkorte, R. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.07.060 · Cited by 62 · see citing works
An ultrasensitive chemical method for polysialic acid analysis
Inoue, S., Lin, S.-J., Lee, Y. C., & Inoue, Y. (2001) · Glycobiology · doi:10.1093/glycob/11.9.759 · Cited by 62 · see citing works
Proteolytic and N -Glycan Processing of Human α 1-Antitrypsin Expressed in Nicotiana benthamiana
Castilho, A., Windwarder, M., Gattinger, P., Mach, L., Strasser, R., Altmann, F., & Steinkellner, H. (2014) · PLANT PHYSIOLOGY · doi:10.1104/pp.114.250720 · Cited by 62 · see citing works
Self-citationProcessing of complex N-glycans in IgG Fc-region is affected by core fucosylation
Castilho, A., Grünwald‐Gruber, C., Thader, A., Oostenbrink, C., Pechlaner, M., Steinkellner, H., & Altmann, F. (2015) · mAbs · doi:10.1080/19420862.2015.1053683 · Cited by 61 · see citing works
Self-citationClose, B. E., Mendiratta, S. S., Geiger, K. M., Broom, L. J., Ho, L., & Colley, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305390200 · Cited by 59 · see citing works
The Impact of N-Glycosylation on the Functions of Polysialyltransferases
Mühlenhoff, M., Manegold, A., Windfuhr, M., Gotza, B., & Gerardy‐Schahn, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101022200 · Cited by 51 · see citing works
Self-citationTsuchiya, A., Lu, W., Weinhold, B., Boulter, L., Stutchfield, B. M., Williams, M. J., Guest, R. V., Minnis-Lyons, S. E., MacKinnon, A. C., Schwarzer, D., et al. (2014) · Hepatology · doi:10.1002/hep.27099 · Cited by 49 · see citing works
Self-citationWerneburg, S., Mühlenhoff, M., Stangel, M., & Hildebrandt, H. (2015) · Glia · doi:10.1002/glia.22815 · Cited by 49 · see citing works
Self-citationSoluble polysialylated NCAM: a novel player of the innate immune system in the lung
Ulm, C., Saffarzadeh, M., Mahavadi, P., Müller, S., Prem, G., Saboor, F., Simon, P., Middendorff, R., Geyer, H., Henneke, I., et al. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1342-0 · Cited by 47 · see citing works
Self-citationSequential Depletion and Acquisition of Proteins during Golgi Stack Disassembly and Reformation
Schoberer, J., Runions, J., Steinkellner, H., Strasser, R., Hawes, C. R., & Osterrieder, A. (2010) · Traffic · doi:10.1111/j.1600-0854.2010.01106.x · Cited by 47 · see citing works
Self-citationWillis, L. M., Gilbert, M., Karwaski, M.-F., Blanchard, M.-C., & Wakarchuk, W. W. (2007) · Glycobiology · doi:10.1093/glycob/cwm126 · Cited by 47 · see citing works
Engineering the product profile of a polysialyltransferase
Keys, T. G., Fuchs, H. L. S., Ehrit, J., Alves, J., Freiberger, F., & Gerardy‐Schahn, R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1501 · Cited by 39 · see citing works
Self-citationEndosialidases: Versatile Tools for the Study of Polysialic Acid
Jakobsson, E., Schwarzer, D., Jokilammi, A., & Finne, J. (2012) · Topics in current chemistry · doi:10.1007/128_2012_349 · Cited by 34 · see citing works
Close, B. E., Wilkinson, J. M., Bohrer, T. J., Goodwin, C. P., Broom, L. J., & Colley, K. (2001) · Glycobiology · doi:10.1093/glycob/11.11.997 · Cited by 34 · see citing works
Polysialic Acid: Overcoming the Hurdles of Drug Delivery
Bader, R. A., & Wardwell, P. R. (2014) · Therapeutic Delivery · doi:10.4155/tde.13.153 · Cited by 26 · see citing works
Site-Specific Glycosylation Profiling Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS)
Grünwald‐Gruber, C., & Altmann, F. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2760-9_27 · Cited by 10 · see citing works
Self-citationLoos, A., & Castilho, A. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2760-9_17 · Cited by 9 · see citing works
Self-citationKojima, N., Tachida, Y., & Tsuji, S. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022173 · Cited by 9 · see citing works
Kaese, M., Galuska, C. E., Simon, P., Braun, B. C., Cabrera-Fuentes, H. A., Middendorff, R., Wehrend, A., Jewgenow, K., & Galuska, S. P. (2015) · FEBS Journal · doi:10.1111/febs.13519 · Cited by 7 · see citing works
Self-citationMass Spectrometric Analysis of Oligo- and Polysialic Acids
Galuska, C. E., Maaß, K., & Galuska, S. P. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2760-9_28 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Impact of host cell line choice on glycan profile
Goh, J. B., & Ng, S. K. (2017) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2017.1416577 · Cited by 226 · see citing works
Plant-based biopharmaceutical engineering
Eidenberger, L., Kogelmann, B., & Steinkellner, H. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00044-6 · Cited by 154 · see citing works
Self-citationAdvanced Plant-Based Glycan Engineering
Montero‐Morales, L., & Steinkellner, H. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00081 · Cited by 135 · see citing works
Self-citationSchoberer, J., & Strasser, R. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.07.005 · Cited by 86 · see citing works
Self-citationDirect quality control of glycoengineered erythropoietin variants
Čaval, T., Tian, W., Yang, Z., Clausen, H., & Heck, A. J. R. (2018) · Nature Communications · doi:10.1038/s41467-018-05536-3 · Cited by 84 · see citing works
Synthetic Glycobiology: Parts, Systems, and Applications
Kightlinger, W., Warfel, K. F., DeLisa, M. P., & Jewett, M. C. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00210 · Cited by 80 · see citing works
Production of complex viral glycoproteins in plants as vaccine immunogens
Margolin, E., Chapman, R. E., Williamson, A., Rybicki, E. P., & Meyers, A. E. (2018) · Plant Biotechnology Journal · doi:10.1111/pbi.12963 · Cited by 75 · see citing works
Tusé, D., Nandi, S., McDonald, K. A., & Buyel, J. F. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.594019 · Cited by 76 · see citing works
Plant synthetic biology could drive a revolution in biofuels and medicine
Mortimer, J. C. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370218793890 · Cited by 70 · see citing works
Improving Protein Quantity and Quality—The Next Level of Plant Molecular Farming
Liu, H., & Timko, M. P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031326 · Cited by 69 · see citing works
Transgene Biocontainment Strategies for Molecular Farming
Clark, M., & Maselko, M. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00210 · Cited by 68 · see citing works
Customized protein glycosylation to improve biopharmaceutical function and targeting
Van Landuyt, L., Lonigro, C., Meuris, L., & Callewaert, N. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.11.017 · Cited by 66 · see citing works
Cellular engineering of plant cells for improved therapeutic protein production
Karki, U., Fang, H., Guo, W., Unnold-Cofre, C., & Xu, J. (2021) · Plant Cell Reports · doi:10.1007/s00299-021-02693-6 · Cited by 65 · see citing works
Engineering the Plant Secretory Pathway for the Production of Next-Generation Pharmaceuticals
Margolin, E., Strasser, R., Chapman, R. E., Williamson, A., Rybicki, E. P., & Meyers, A. E. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.03.004 · Cited by 58 · see citing works
Self-citationCastilho, A., Beihammer, G., Pfeiffer, C., Göritzer, K., Montero‐Morales, L., Vavra, U., Maresch, D., Grünwald‐Gruber, C., Altmann, F., Steinkellner, H., et al. (2018) · Plant Biotechnology Journal · doi:10.1111/pbi.12906 · Cited by 57 · see citing works
Self-citationN- and O-Glycosylation Pathways in the Microalgae Polyphyletic Group
Mathieu‐Rivet, E., Mati‐Baouche, N., Walet-Balieu, M.-L., Lerouge, P., & Bardor, M. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.609993 · Cited by 55 · see citing works
Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation
Thiesler, H., Beimdiek, J., & Hildebrandt, H. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03601-z · Cited by 55 · see citing works
Self-citationTransient Production of Recombinant Pharmaceutical Proteins in Plants: Evolution and Perspectives
Kopertekh, L., & Schiemann, J. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170718114724 · Cited by 50 · see citing works
Targeted genome editing of plants and plant cells for biomanufacturing
Buyel, J. F., Stöger, E., & Bortesi, L. (2021) · Transgenic Research · doi:10.1007/s11248-021-00236-z · Cited by 51 · see citing works
Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies
Tytgat, H. L. P., Lin, C., Levasseur, M. D., Tomek, M. B., Rutschmann, C., Mock, J., Liebscher, N., Terasaka, N., Azuma, Y., Wetter, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13283-2 · Cited by 45 · see citing works
Plant glycoengineering for designing next-generation vaccines and therapeutic proteins
Strasser, R. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108197 · Cited by 43 · see citing works
Self-citationPlant-Based Vaccines: The Way Ahead?
LeBlanc, Z., Waterhouse, P. M., & Bally, J. (2020) · Viruses · doi:10.3390/v13010005 · Cited by 44 · see citing works
Exploring the Glycans of Euglena gracilis
O’Neill, E. C., Kuhaudomlarp, S., Rejzek, M., Fangel, J. U., Alagesan, K., Kolarich, D., Willats, W. G. T., & Field, R. A. (2017) · Biology · doi:10.3390/biology6040045 · Cited by 42 · see citing works
Gupta, M. D., Flaskamp, Y., Roentgen, R., Juergens, H., Armero‐Gimenez, J., Albrecht, F., Hemmerich, J., Arfi, Z. A., Neuser, J., Spiegel, H., et al. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28461 · Cited by 41 · see citing works
Engineering of Plants for Efficient Production of Therapeutics
Sethi, L., Kumari, K., & Dey, N. (2021) · Molecular Biotechnology · doi:10.1007/s12033-021-00381-0 · Cited by 41 · see citing works
Goulet, M., Gaudreau, L., Gagné, M., Maltais, A.-M., Laliberté, A., Éthier, G., Bechtold, N., Martel, M., D’Aoust, M., Gosselin, A., et al. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2019.00735 · Cited by 40 · see citing works
Glycoengineering design options for IgG1 in CHO cells using precise gene editing
Schulz, M. A., Tian, W., Mao, Y., Coillie, J. V., Sun, L., Larsen, J. S., Chen, Y., Kristensen, C., Vakhrushev, S. Y., Clausen, H., et al. (2018) · Glycobiology · doi:10.1093/glycob/cwy022 · Cited by 39 · see citing works
A biosynthetic route for polysialylating proteins in Escherichia coli
Keys, T. G., Wetter, M., Hang, I., Rutschmann, C., Russo, S., Mally, M., Steffen, M., Zuppiger, M., Müller, F., Schneider, J., et al. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.10.012 · Cited by 37 · see citing works
NMR of glycoproteins: profiling, structure, conformation and interactions
Unione, L., Ardá, A., Jiménez‐Barbero, J., & Millet, Ó. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.09.009 · Cited by 37 · see citing works
Glycoengineering of plants yields glycoproteins with polysialylation and other defined N-glycoforms
Chen, Q. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610803113 · Cited by 37 · see citing works
BGAL1 depletion boosts the level of β‐galactosylation of N‐ and O‐glycans in N. benthamiana
Kriechbaum, R., Ziaee, E., Grünwald‐Gruber, C., Buscaill, P., van der Hoorn, R. A. L., & Castilho, A. (2019) · Plant Biotechnology Journal · doi:10.1111/pbi.13316 · Cited by 34 · see citing works
Self-citationCompendium on Food Crop Plants as a Platform for Pharmaceutical Protein Production
Gerszberg, A., & Hnatuszko-Konka, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063236 · Cited by 33 · see citing works
Sukenick, S., Karuppanan, K., Li, Q., Lebrilla, C. B., Nandi, S., & McDonald, K. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041205 · Cited by 33 · see citing works
Thiesler, H., Küçükerden, M., Gretenkort, L., Röckle, I., & Hildebrandt, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.871757 · Cited by 32 · see citing works
Self-citationRecent advances in expression and purification strategies for plant made vaccines
Venkataraman, S., Khan, I. H., Habibi, P., Le, M., Lippert, R., & Hefferon, K. L. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1273958 · Cited by 31 · see citing works
Rozov, S. M., Permyakova, N. V., & Deineko, E. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918030033 · Cited by 26 · see citing works
Margolin, E., Crispin, M., Meyers, A. E., Chapman, R. E., & Rybicki, E. P. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.609207 · Cited by 29 · see citing works
Ridgley, L. A., Finardi, N. F., Gengenbach, B. B., Opdensteinen, P., Croxford, Z., K‐C., J., Bodman‐Smith, M. D., Buyel, J. F., & Teh, A. Y. (2023) · Plant Biotechnology Journal · doi:10.1111/pbi.14034 · Cited by 29 · see citing works
Stable Protein Sialylation in Physcomitrella
Bohlender, L. L., Parsons, J., Hoernstein, S. N. W., Rempfer, C., Ruiz-Molina, N., Lorenz, T., Rodríguez-Jahnke, F., Figl, R., Fode, B., Altmann, F., et al. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.610032 · Cited by 28 · see citing works
Self-citationImmunoglobulin A Glycosylation and Its Role in Disease
Hansen, A. L., Reily, C., Novák, J., & Renfrow, M. B. (2021) · Experientia supplementum · doi:10.1007/978-3-030-76912-3_14 · Cited by 26 · see citing works
mAbs N-glycosylation: Implications for biotechnology and analytics
Wang, T., Liu, L., & Voglmeir, J. (2022) · Carbohydrate Research · doi:10.1016/j.carres.2022.108541 · Cited by 26 · see citing works
Diakomanolis, E., Haidopoulos, D., Syndos, M., Rodolakis, A., Stefanidis, K., Chatzipapas, J., & Michalas, S. (2002) · PubMed · Cited by 26 · see citing works
Santos, L. N., Pacheco, L. G. C., Pinheiro, C. S., & Alcântara‐Neves, N. M. (2016) · Acta Tropica · doi:10.1016/j.actatropica.2016.11.016 · Cited by 24 · see citing works
In Planta Glycan Engineering and Functional Activities of IgE Antibodies
Montero‐Morales, L., Maresch, D., Crescioli, S., Castilho, A., Ilieva, K. M., Mele, S., Karagiannis, S. N., Altmann, F., & Steinkellner, H. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00242 · Cited by 24 · see citing works
Self-citationOptimizing product quality in molecular farming
Schiermeyer, A. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.08.012 · Cited by 22 · see citing works
Transient Expression of Glycosylated SARS-CoV-2 Antigens in Nicotiana benthamiana
Ruocco, V., & Strasser, R. (2022) · Plants · doi:10.3390/plants11081093 · Cited by 23 · see citing works
Self-citationKogelmann, B., Melnik, S., Bogner, M., Kallolimath, S., Stöger, E., Sun, L., Strasser, R., D’Aoust, M., Lavoie, P., Saxena, P., et al. (2023) · Biotechnology Journal · doi:10.1002/biot.202300323 · Cited by 21 · see citing works
Self-citationGlyco-Engineering of Plant-Based Expression Systems
Fischer, R., Holland, T., Sack, M., Schillberg, S., Stöger, E., Twyman, R. M., & Buyel, J. F. (2018) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2018_76 · Cited by 21 · see citing works
Teh, A. Y., Cavacini, L. A., Hu, Y., Kumru, O. S., Xiong, J., Bolick, D. T., Joshi, S. B., Grünwald‐Gruber, C., Altmann, F., Klempner, M. S., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2020.1859813 · Cited by 20 · see citing works
Self-citationExpression Profiling and Glycan Engineering of IgG Subclass 1–4 in Nicotiana benthamiana
Kallolimath, S., Hackl, T., Gahn, R., Grünwald‐Gruber, C., Zich, W., Kogelmann, B., Lux, A., Nimmerjahn, F., & Steinkellner, H. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00825 · Cited by 19 · see citing works
Self-citationUnexpected Arabinosylation after Humanization of Plant Protein N-Glycosylation
Bohlender, L. L., Parsons, J., Hoernstein, S. N. W., Bangert, N., Rodríguez-Jahnke, F., Ralf Reski, A., & Decker, E. L. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.838365 · Cited by 18 · see citing works
Engineering Approaches in Plant Molecular Farming for Global Health
Singh, A. A., Pillay, P., & Tsekoa, T. L. (2021) · Vaccines · doi:10.3390/vaccines9111270 · Cited by 17 · see citing works
Comparative analysis of plant transient expression vectors for targeted N-glycosylation
Eidenberger, L., Eminger, F., Castilho, A., & Steinkellner, H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1073455 · Cited by 16 · see citing works
Self-citationKittur, F. S., Hung, C., Zhu, C., Shajahan, A., Azadi, P., Thomas, M. D., Pearce, J. L., Grünwald‐Gruber, C., Kallolimath, S., & Xie, J. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.04.199 · Cited by 16 · see citing works
Self-citationFukuzawa, N., Matsuo, K., Atsumi, G., Tasaka, Y., & Mitsuda, N. (2024) · Plant Biotechnology · doi:10.5511/plantbiotechnology.24.0716a · Cited by 15 · see citing works
Neuroimmunomodulatory properties of polysialic acid
Gretenkort, L., Thiesler, H., & Hildebrandt, H. (2023) · Glycoconjugate Journal · doi:10.1007/s10719-023-10120-z · Cited by 15 · see citing works
Self-citationProduction of therapeutic glycoproteins in glycoengineered plant: old farm for new crops
Kao, M., Saldivar, R. K., & Hsieh, Y. S. Y. (2024) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2024.103145 · Cited by 13 · see citing works
Gołębiowski, A., Szultka‐Młyńska, M., Pomastowski, P., Rafińska, K., Orzoł, A., Cichorek, M., Olszewski, J., Buszewski, B., & Głowacka, K. (2024) · Journal of soil science and plant nutrition · doi:10.1007/s42729-024-01929-0 · Cited by 13 · see citing works
A central role for polyprenol reductase in plant dolichol biosynthesis
Gelder, K. V., Virta, L. K. A., Easlick, J., Prudhomme, N., McAlister, J. A., Geddes‐McAlister, J., & Akhtar, T. A. (2020) · Plant Science · doi:10.1016/j.plantsci.2020.110773 · Cited by 13 · see citing works
Allard, J. L., Shields, K. A., Munro, T. P., & Lua, L. H. L. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.109996 · Cited by 13 · see citing works
Trafficking and localization of Golgi-resident N-glycan processing enzymes in plants
Dünser, K., & Schoberer, J. (2025) · Frontiers in Plant Science · doi:10.3389/fpls.2025.1624949 · Cited by 12 · see citing works
Dumontier, R., Mareck, A., Mati‐Baouche, N., Lerouge, P., & Bardor, M. (2018) · InTech eBooks · doi:10.5772/intechopen.73401 · Cited by 12 · see citing works
N-Glycosylation of Plant Proteins
Алексеевна, Л. И., Fedina, E. O., Mikshina, P. V., & Gorshkova, T. (2024) · Russian Journal of Plant Physiology · doi:10.1134/s1021443724604555 · Cited by 11 · see citing works
Leprovost, S., Plasson, C., Balieu, J., Walet‐Balieu, M., Lerouge, P., Bardor, M., & Mathieu‐Rivet, E. (2024) · Plant Biotechnology Journal · doi:10.1111/pbi.14424 · Cited by 11 · see citing works
Plant production systems for recombinant immunotherapeutic proteins
Jin, C., Hinterdorfer, P., Lee, J. H., & Ko, K. (2025) · Plant Biotechnology Reports · doi:10.1007/s11816-024-00956-8 · Cited by 10 · see citing works
Production and N-glycan engineering of Varlilumab in Nicotiana benthamiana
Nguyen, K. D., Kajiura, H., Kamiya, R., Yoshida, T., Misaki, R., & Fujiyama, K. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1215580 · Cited by 10 · see citing works
Assessment of transient expression strategies to sialylate recombinant proteins in N. benthamiana
Izadi, S., Kunnummel, V., Steinkellner, H., Werner, S., & Castilho, A. (2023) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2023.02.004 · Cited by 10 · see citing works
Self-citationGupta, M. D., Flaskamp, Y., Roentgen, R., Juergens, H., Armero‐Gimenez, J., Albrecht, F., Hemmerich, J., Arfi, Z. A., Neuser, J., Spiegel, H., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.10.515920 · Cited by 10 · see citing works
Posttranslational modifications of heterologous proteins expressed in Nicotiana benthamiana
Göritzer, K., Kallolimath, S., & Strasser, R. (2025) · Plant Biotechnology Journal · doi:10.1111/pbi.70176 · Cited by 9 · see citing works
Self-citationGlycosylation of Plant-Produced Immunoglobulins
Göritzer, K., & Strasser, R. (2021) · Experientia supplementum · doi:10.1007/978-3-030-76912-3_16 · Cited by 8 · see citing works
Self-citation125 years of virology and ascent of biotechnologies based on viral expressio
Giritch, A., Klimyuk, V. I., & Gleba, Y. Y. (2017) · Cytology and Genetics · doi:10.3103/s0095452717020037 · Cited by 8 · see citing works
Engineering Mammalian Cells to Produce Plant-Specific N-glycosylation on Proteins.
Larsen, J. S., Karlsson, R., Tian, W.-H., Schulz, M. A., Matthes, A., Clausen, H., Petersen, B., & Yang, Z. (2020) · Glycobiology · doi:10.1093/glycob/cwaa009 · Cited by 6 · see citing works
Frontiers in the Standardization of the Plant Platform for High Scale Production of Vaccines
Citiulo, F., Crosatti, C., Cattivelli, L., & Biselli, C. (2021) · Plants · doi:10.3390/plants10091828 · Cited by 7 · see citing works
Producing Biologics with Defined N-Glycosylation in Plants
Esqueda, A., & Chen, Q. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2835-5_17 · Cited by 6 · see citing works
Uetz, P., Göritzer, K., Vergara, E. J., Melnik, S., Grünwald‐Gruber, C., Figl, R., Deghmane, A., Groppelli, E., Reljić, R., K‐C., J., et al. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1329018 · Cited by 6 · see citing works
Self-citationEfficient Expression of Functionally Active Aflibercept with Designed N-glycans
Keshvari, T., Melnik, S., Sun, L., Niazi, A., Aram, F., Moghadam, A. A., Kogelmann, B., Wozniak‐Knopp, G., Kallolimath, S., Ramezani, A., et al. (2024) · Antibodies · doi:10.3390/antib13020029 · Cited by 6 · see citing works
Self-citationAdvances and challenges in plant N-glycoengineering: when fucosylation matters
Gauba, K., Kunnummel, V., & Castilho, A. (2025) · Frontiers in Plant Science · doi:10.3389/fpls.2025.1734060 · Cited by 5 · see citing works
Self-citationMorel, B., Favrot, C., Mirande, L., Grünwald‐Gruber, C., Stordeur, V., Vezina, L. P., Faye, L. J.-Y., & Gomord, V. (2024) · Vaccines · doi:10.3390/vaccines12060620 · Cited by 4 · see citing works
Self-citationDianatkhah, S., Kogelmann, B., Melnik, S., Eminger, F., Kallolimath, S., Sun, L., Sumesgutner, D., Traxlmayr, M. W., Sack, M., Stöger, E., et al. (2025) · Plant Biotechnology Journal · doi:10.1111/pbi.70044 · Cited by 4 · see citing works
Self-citationReteplase Fc-fusions produced in N. benthamiana are able to dissolve blood clots ex vivo
Izadi, S., Javaran, M. J., Monfared, S. R., & Castilho, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260796 · Cited by 4 · see citing works
Self-citationXylosylation of proteins by expression of human xylosyltransferase 2 in plants
Matsuo, K., & Atsumi, G. (2018) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2018.03.013 · Cited by 4 · see citing works
Production of Functionally Active Recombinant Proteins in Plants
Castilho, A., & Strasser, R. (2018) · Wiley eBooks · doi:10.1002/9781118801512.ch4 · Cited by 4 · see citing works
Self-citationNajafi, K., Jojani, M., Najafi, S., & Roviello, G. (2026) · Vaccines · doi:10.3390/vaccines14050391 · Cited by 3 · see citing works
Seed-Based Production of Recombinant Proteins
Lacorte, C. C., Ferreira, A. L., Murad, A. M., da Cunha, N. B., & Pinheiro, P. (2023) · Concepts and strategies in plant sciences · doi:10.1007/978-981-99-4859-8_6 · Cited by 2 · see citing works
Sialoglycans and genetically engineered plants
Ghosh, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816126-5.00002-0 · Cited by 2 · see citing works
Production of Complex Proteins in Plants: From Farming to Manufacturing
Nausch, H., Knödler, M., & Buyel, J. F. (2023) · Cell engineering · doi:10.1007/978-3-031-45669-5_8 · Cited by 2 · see citing works
Rani, D., & Vimolmangkang, S. (2024) · Concepts and strategies in plant sciences · doi:10.1007/978-981-97-0176-6_6 · Cited by 2 · see citing works
Bataa, D., Kajiura, H., Sawada‐Choi, R. L. S., Yamashita, Y., Ishimizu, T., Misaki, R., Takeda, A., & Fujiyama, K. (2025) · Plant Biotechnology Journal · doi:10.1111/pbi.70326 · Cited by 1 · see citing works
Sweers, M. R., Wilbers, R. H. P., Schots, A., & Nibbering, P. (2026) · New Biotechnology · doi:10.1016/j.nbt.2026.01.014 · Cited by 1 · see citing works
N-Glycoengineering of insect cells for tri-antennary N-glycan biosynthesis
Kajiura, H., Nishiguchi, N., Sawada‐Choi, R. L. S., Sana, Y., Misaki, R., & Fujiyama, K. (2026) · Scientific Reports · doi:10.1038/s41598-026-41152-8 · Cited by 1 · see citing works
Beyond Starch: Towards a Scalable Potato Platform for Molecular Farming
Chincinska, I., Sołtys‐Kalina, D., & Teh, A. Y. (2026) · Plant Biotechnology Journal · doi:10.1111/pbi.70616 · Cited by 1 · see citing works
Polysialic Acid Synthesis on the N - and O -Glycans of Salmonid Polysialyltransferase ST8Sia IV
Seidel, A., Decloquement, M., Sun, L., Vicogne, D., Günther, J., Galuska, C. E., Kallolimath, S., Galuska, S. P., & Harduin‐Lepers, A. (2026) · ACS Omega · doi:10.1021/acsomega.5c12731 · Cited by 1 · see citing works
Self-citationMeyers, A. J., Grohs, B. M., & Hall, J. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-444-64046-8.00226-3 · Cited by 1 · see citing works
Contemporary and Emerging Technologies for Precise N‐glycan Analyses
Wilson, I., Paschinger, K., Vanbeselaere, J., & Jin, C. (2018) · doi:10.1002/9781118801512.ch3
Bartling, B., Brüchle, N. C., Rehfeld, J. S., Boßmann, D., Fiebig, T., Litschko, C., Fohrer, J., Gerardy‐Schahn, R., Scheper, T. H., & Beutel, S. (2020) · Biotechnology Reports · doi:10.1016/j.btre.2020.e00562
Self-citationOptimization of Biopharming Systems in Nicotiana benthamiana
LeBlanc, Z. (2022) · Queensland University of Technology · doi:10.5204/thesis.eprints.227853
Chhikara, M. K. (2019) · Journal of Bacteriology & Mycology Open Access · doi:10.15406/jbmoa.2019.07.00251
Seed-Based Production System for Molecular Farming
Takaiwa, F. (2023) · Concepts and strategies in plant sciences · doi:10.1007/978-981-99-4859-8_5
- Authors
- Kallolimath, S., Castilho, A., Strasser, R., Grünwald-Gruber, C., Altmann, F., Strubl, S., Galuska, C. E., Zlatina, K., Galuska, S. P., Werner, S., Thiesler, H., Werneburg, S., Hildebrandt, H., Gerardy-Schahn, R., & Steinkellner, H.
- Affiliations
- BOKU University (AT)
- Department of Chemistry, University of Natural Resources and Life Sciences, 1190 Vienna, Austria;
- Justus-Liebig-Universität Gießen (DE)
- Nambawan Biotech GmbH, D-06120 Halle/Saale, Germany;
- Medizinische Hochschule Hannover (DE)
- Institute for Cellular Chemistry, Hannover Medical School, 30625 Hannover, Germany
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-07-21
- Volume
- 113
- Issue
- 34
- Pages
- 9498-9503
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5003249
- OpenAlex
- W2489417518
- Cited by
- 113
- References
- 59
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 12 · 2023: 12 · 2022: 11 · 2021: 9 · 2020: 18 · 2019: 8 · 2018: 14 · 2017: 7 · 2016: 2
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-05-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GA 1755/1-2)
- Österreichische Forschungsförderungsgesellschaft (822757)
- Austrian Science Fund (FWF L575-B13 and TRP 242-B20)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Transgenic Plants and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- sialic acid, polysialic acid, plant-based expression systems, transient expression, degree of polymerization, glycoproteins, microglial activation, cytotoxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
