RNA interference of sialidase improves glycoprotein sialic acid content consistency
Abstract
An important challenge facing therapeutic protein production in mammalian cell culture is the cleavage of terminal sialic acids on recombinant protein glycans by the glycosidase enzymes released by lysed cells into the supernatant. This undesired phenomenon results in a protein product which is rapidly cleared from the plasma by asialoglycoprotein receptors in the liver. In this study, RNA interference was utilized as a genetic approach to silence the activity of sialidase, a glycosidase responsible for cleaving terminal sialic acids on IFN‐γ produced by Chinese Hamster Ovary (CHO) cells. We first identified a 21‐nt double stranded siRNA that reduced endogenous sialidase mRNA and protein activity levels. Potency of each siRNA sequences was compared using real time RT‐PCR and a sialidase activity assay. We next integrated the siRNA sequence into CHO cells, allowing production and selection of stable cell lines. We isolated stable clones with sialidase activity reduced by over 60% as compared to the control cell line. Micellar electrokinetic chromatography (MEKC), thiobarbituric acid assay (TAA), and high performance anion exchange chromatography (HPAEC) coupled to amperometric detection were performed to analyze glycan site occupancy, sialic acid content, and distribution of asialo‐/sialylated‐glycan structures, respectively. Two of the stable clones successfully retained the full sialic acid content of the recombinant IFN‐γ, even upon cells' death. This was comparable to the case where a chemically synthesized sialidase inhibitor was used. These results demonstrated that RNA interference of sialidase can prevent the desialylation problem in glycoprotein production, resulting improved protein quality during the entire cell culture process. © 2006 Wiley Periodicals, Inc.
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?
Some attempts of knocking down the different CHO sialidases by shRNA or siRNA also improved the sialylation level of recombinant hIFNγ, particularly for Neu2 and Neu3 sialidases.
“Some attempts of knocking down the different CHO sialidases by shRNA or siRNA also improved the sialylation level of recombinant hIFNγ, particularly for Neu2 and Neu3 sialidases (Ngantung et al., 2006;Zhang et al., 2010b).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Ngantung et al., 2006
Cites
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
ASSEMBLY OF ASPARAGINE-LINKED OLIGOSACCHARIDES
Kornfeld, R., & Kornfeld, S. A. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.003215 · Cited by 4,863 · see citing works
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · see citing works
Production of recombinant protein therapeutics in cultivated mammalian cells
Wurm, F. M. (2004) · Nature Biotechnology · doi:10.1038/nbt1026 · Cited by 2,032 · see citing works
Carbohydrate-Specific Receptors of the Liver
Ashwell, G., & Harford, J. (1982) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.51.070182.002531 · Cited by 1,914 · see citing works
Killing the messenger: short RNAs that silence gene expression
Dykxhoorn, D. M., Novina, C., & Sharp, P. (2003) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1129 · Cited by 1,290 · see citing works
Chemical Diversity in the Sialic Acids and Related α-Keto Acids: An Evolutionary Perspective
Angata, T., & Varki, A. P. (2002) · Chemical Reviews · doi:10.1021/cr000407m · Cited by 1,232 · see citing works
Analysis of gene function in somatic mammalian cells using small interfering RNAs
Elbashir, S. M. (2002) · Methods · doi:10.1016/s1046-2023(02)00023-3 · Cited by 1,094 · see citing works
siRNA-mediated gene silencing in vitro and in vivo
Xia, H., Mao, Q., Paulson, H. L., & Davidson, B. L. (2002) · Nature Biotechnology · doi:10.1038/nbt739 · Cited by 873 · see citing works
Novina, C. D., & Sharp, P. A. (2004) · Nature · doi:10.1038/430161a · Cited by 730 · see citing works
CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris
Abrams, J. R., Lebwohl, M., Guzzo, C. A., Jegasothy, B. V., Goldfarb, M. T., Goffe, B. S., Menter, A., Lowe, N. J., Krueger, G. G., Brown, M. J. C., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5857 · Cited by 597 · see citing works
Development and characterization of novel erythropoiesis stimulating protein (NESP)
Egrie, J. C., & Browne, J. K. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1746 · Cited by 514 · see citing works
Sialic acids: fascinating sugars in higher animals and man
Schauer, R. (2004) · Zoology · doi:10.1016/j.zool.2003.10.002 · Cited by 415 · see citing works
Survival of recombinant erythropoietin in the circulation: the role of carbohydrates
Fukuda, M., Sasaki, H., Lopez, L. B., & Fukuda, M. (1989) · Blood · doi:10.1182/blood.v73.1.84.84 · Cited by 386 · see citing works
Glacken, M. W., Fleischaker, R. J., & Sinskey, A. J. (1986) · Biotechnology and Bioengineering · doi:10.1002/bit.260280912 · Cited by 348 · see citing works
Glycobiology : a practical approach
Kobata, A., & Fukuda, M. (1993) · Oxford University Press eBooks · Cited by 339 · see citing works
Powerful and versatile enhancer-promoter unit for mammalian expression vectors
Foecking, M. K., & Hofstetter, H. (1986) · Gene · doi:10.1016/0378-1119(86)90137-x · Cited by 269 · see citing works
Glycosylation of recombinant proteins: Problems and prospects
Jenkins, N., & Curling, E. M. A. (1994) · Enzyme and Microbial Technology · doi:10.1016/0141-0229(94)90149-x · Cited by 244 · see citing works
Yoon, S. K., Song, J. Y., & Lee, G. M. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10566 · Cited by 244 · see citing works
Wong, D. C. F., Wong, K. T. K., Goh, L. T., Heng, C., & Yap, M. G. S. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20317 · Cited by 231 · see citing works
Matthijs, H. C. P., Balke, H., van Hes, U. M., Kroon, B. M. A., Mur, L. R., & Binot, R. A. (1996) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(19960405)50:1 · Cited by 226 · see citing works
The in vivo metabolism of recombinant human erythropoietin in the rat
Spivak, J., & Hogans, B. (1989) · Blood · doi:10.1182/blood.v73.1.90.bloodjournal73190 · Cited by 179 · see citing works
Sodetz, J. M., Pizzo, S. V., & McKee, P. A. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63384-3 · Cited by 179 · see citing works
Mori, K., Kuni‐Kamochi, R., Yamane‐Ohnuki, N., Wakitani, M., Yamano, K., Imai, H., Kanda, Y., Niwa, R., Iida, S., Uchida, K., et al. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20326 · Cited by 174 · see citing works
Hammond, K., & Papermaster, D. S. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90210-4 · Cited by 170 · see citing works
Glycosidase Activities in Chinese Hamster Ovary Cell Lysate and Cell Culture Supernatant
Gramer, M. J., & Goochee, C. F. (1993) · Biotechnology Progress · doi:10.1021/bp00022a003 · Cited by 136 · see citing works
Gramer, M. J., Goochee, C. F., Chock, V. Y., Brousseau, D. T., & Sliwkowski, M. B. (1995) · Nature Biotechnology · doi:10.1038/nbt0795-692 · Cited by 107 · see citing works
Bragonzi, A., Distefano, G., Buckberry, L. D., Acerbis, G., Foglieni, C., Lamotte, D., Campi, G., Marc, A., Soria, M. R., Jenkins, N., et al. (2000) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(00)00023-4 · Cited by 96 · see citing works
Yoshikawa, T., Nakanishi, F., Ogura, Y., Oi, D. H., Ōmasa, T., Katakura, Y., Kishimoto, M., & Suga, K. (2000) · Biotechnology Progress · doi:10.1021/bp000114e · Cited by 94 · see citing works
Hansen, H. A., & Emborg, C. (1994) · Biotechnology Progress · doi:10.1021/bp00025a014 · Cited by 90 · see citing works
Kato, T., Wang, Y., Yamaguchi, K., Milner, C. M., Shineha, R., Satomi, S., & Miyagi, T. (2001) · International Journal of Cancer · doi:10.1002/ijc.1268 · Cited by 71 · see citing works
Involvement of an Endogenous Sialidase in Skeletal Muscle Cell Differentiation
Sato, K., & Miyagi, T. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0681 · Cited by 70 · see citing works
Genetic engineering of CHO cells producing human interferon-γ by transfection of sialyltransferases
Fukuta, K., Yokomatsu, T., Abe, R., Asanagi, M., & Makino, T. (2000) · Glycoconjugate Journal · doi:10.1023/a:1010977431061 · Cited by 62 · see citing works
In vivo bioactivities and clearance patterns of highly purified human luteinizing hormone isoforms.
Burgon, P. G., Stanton, P. G., & Robertson, D. M. (1996) · Endocrinology · doi:10.1210/endo.137.11.8895353 · Cited by 62 · see citing works
Warner, T. G., Chang, J., Ferrari, J., Harris, R., McNerney, T., Bennett, G., Burnier, J., & Sliwkowski, M. B. (1993) · Glycobiology · doi:10.1093/glycob/3.5.455 · Cited by 59 · see citing works
The cellular basis for liver injury in α1‐antitrypsin deficiency
Perlmutter, D. H. (1991) · Hepatology · doi:10.1002/hep.1840130125 · Cited by 58 · see citing works
Saxena, A., Raveh, L., Ashani, Y., & Doctor, B. P. (1997) · Biochemistry · doi:10.1021/bi963156d · Cited by 55 · see citing works
Flesher, A. R., Marzowski, J., Wang, W., & Raff, H. V. (1995) · Biotechnology and Bioengineering · doi:10.1002/bit.260460502 · Cited by 55 · see citing works
Gramer, M. J., & Goochee, C. F. (1994) · Biotechnology and Bioengineering · doi:10.1002/bit.260430510 · Cited by 44 · see citing works
Blood clotting factor IX. Loss of activity after cleavage of sialic acid residues.
Chavin, S. I., & Weidner, S. M. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43103-6 · Cited by 39 · see citing works
Malphettes, L., & Fussenegger, M. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20230 · Cited by 26 · see citing works
Carlsen, M., Jokumsen, K. V., Emborg, C., & Nielsen, J. (1997) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(19970720)55:2 · Cited by 24 · see citing works
Self-citationAnalysis of Nonderivatized Neutral and Sialylated Oligosaccharides by Electrospray Mass Spectrometry
Huang, L., & Riggin, R. M. (2000) · Analytical Chemistry · doi:10.1021/ac0001378 · Cited by 24 · see citing works
Williams, B. A., Makrigiannis, A. P., Blay, J., & Hoskin, D. W. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19971104)73:3 · Cited by 22 · see citing works
Watari (1997) · International Journal of Hematology · doi:10.1016/s0925-5710(97)00576-8 · Cited by 19 · see citing works
Mortensen, B., & Huseby, N. (1997) · Clinica Chimica Acta · doi:10.1016/s0009-8981(96)06427-3 · Cited by 16 · see citing works
Catabolism of desialylated human plasma α1-antitrypsin and its trypsin complex in the rat
Gan, J. C. (1979) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(79)90604-0 · Cited by 9 · see citing works
Fox, S. R. (2005) · Cited by 4 · see citing works
Batta, S. K., Rabovsky, M. A., Channing, C. P., & Bahl, O. P. (1979) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-3474-3_84 · Cited by 3 · see citing works
Glycosylation site occupancy heterogeneity in Chinese hamster ovary cell culture
Nyberg, G. B. (1998) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 3 · see citing works
- Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The art of CHO cell engineering: A comprehensive retrospect and future perspectives
Fischer, S., Handrick, R., & Otte, K. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.10.015 · Cited by 314 · see citing works
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
Monti, E., Bonten, E. J., d’Azzo, A., Bresciani, R., Venerando, B., Borsani, G., Schauer, R., & Tettamanti, G. (2010) · Advances in carbohydrate chemistry and biochemistry · doi:10.1016/s0065-2318(10)64007-3 · Cited by 201 · see citing works
Bork, K., Horstkorte, R., & Weidemann, W. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21684 · Cited by 177 · see citing works
Capillary electrophoresis of proteins 2005–2007
Dolnı́k, V. (2007) · Electrophoresis · doi:10.1002/elps.200700584 · Cited by 165 · see citing works
Harvey, D. J. (2006) · Mass Spectrometry Reviews · doi:10.1002/mas.20080 · Cited by 153 · see citing works
N-Glycosylation Design and Control of Therapeutic Monoclonal Antibodies
Sha, S., Agarabi, C. D., Brorson, K., Lee, D., & Yoon, S. (2016) · Trends in biotechnology · doi:10.1016/j.tibtech.2016.02.013 · Cited by 149 · see citing works
Byrne, B. J., Donohoe, G. G., & O’Kennedy, R. J. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.02.010 · Cited by 148 · see citing works
Wong, N. S. C., Wati, L., Nissom, P. M., Feng, H., Lee, M. M., & Yap, M. G. S. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22812 · Cited by 142 · see citing works
Engineering mammalian cells in bioprocessing – current achievements and future perspectives
Lim, Y., Wong, N. S. C., Lee, Y. Y., Ku, S. C. Y., Wong, D. C. F., & Yap, M. G. S. (2010) · Biotechnology and Applied Biochemistry · doi:10.1042/ba20090363 · Cited by 134 · see citing works
An 'omics approach towards CHO cell engineering
Datta, P., Linhardt, R. J., & Sharfstein, S. T. (2013) · Biotechnology and Bioengineering · doi:10.1002/bit.24841 · Cited by 129 · see citing works
Harvey, D. J. (2010) · Mass Spectrometry Reviews · doi:10.1002/mas.20265 · Cited by 98 · see citing works
Features and applications of bacterial sialidases
Kim, S., Oh, D., Kang, H. A., & Kwon, O. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3307-2 · Cited by 87 · see citing works
Engineering host cell lines to reduce terminal sialylation of secreted antibodies
Naso, M. F., Tam, S. H., Scallon, B. J., & Raju, T. S. (2010) · mAbs · doi:10.4161/mabs.2.5.13078 · Cited by 74 · see citing works
Lin, N., Mascarenhas, J., Sealover, N. R., George, H. J., Brooks, J., Kayser, K. J., Gau, B., Yasa, I., Azadi, P., & Archer‐Hartmann, S. (2015) · Biotechnology Progress · doi:10.1002/btpr.2038 · Cited by 73 · see citing works
Son, Y.-D., Jeong, Y. T., Park, S.-Y., & Kim, J. H. (2011) · Glycobiology · doi:10.1093/glycob/cwr034 · Cited by 73 · see citing works
Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells
Zhang, M., Koskie, K., Ross, J. S., Kayser, K. J., & Caple, M. V. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22633 · Cited by 62 · see citing works
Methods in mammalian cell line engineering: from random mutagenesis to sequence-specific approaches
Krämer, O., Klausing, S., & Noll, T. (2010) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-010-2798-6 · Cited by 61 · see citing works
Product Quality Considerations for Mammalian Cell Culture Process Development and Manufacturing
Gramer, M. J. (2013) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2013_214 · Cited by 54 · see citing works
Glyco-biosensors: Recent advances and applications for the detection of free and bound carbohydrates
Cunningham, S., Gerlach, J. Q., Kane, M., & Joshi, L. (2010) · The Analyst · doi:10.1039/c0an00276c · Cited by 54 · see citing works
Hebert, C. G., Valdés, J. J., & Bentley, W. E. (2008) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2008.08.006 · Cited by 54 · see citing works
Profiling of N‐glycosylation gene expression in CHO cell fed‐batch cultures
Wong, D. C. F., Wong, N. S. C., Goh, J. S. Y., May, L. M., & Yap, M. G. S. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22828 · Cited by 53 · see citing works
Zhong, X., & Wright, J. F. (2013) · International Journal of Cell Biology · doi:10.1155/2013/273086 · Cited by 48 · see citing works
Mabashi-Asazuma, H., Kuo, C.-W., Khoo, K., & Jarvis, D. (2014) · Glycobiology · doi:10.1093/glycob/cwt161 · Cited by 43 · see citing works
Majumdar, S., Desai, R., Hans, A. K., Dandekar, P. P., & Jain, R. D. (2024) · Molecular Biotechnology · doi:10.1007/s12033-024-01060-6 · Cited by 43 · see citing works
Toth, A. M., Kuo, C., Khoo, K., & Jarvis, D. L. (2014) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2014.04.011 · Cited by 42 · see citing works
Comparative study of idursulfase beta and idursulfase in vitro and in vivo
Kim, C., Seo, J., Chung, Y.-K., Ji, H.-J., Lee, J., Sohn, J., Lee, B., & Jo, E. (2016) · Journal of Human Genetics · doi:10.1038/jhg.2016.133 · Cited by 41 · see citing works
Glycoengineering of CHO Cells to Improve Product Quality
Wang, Q., Yin, B., Chung, C., & Betenbaugh, M. J. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6972-2_2 · Cited by 40 · see citing works
A high-throughput method for quantification of glycoprotein sialylation
Markely, L. R. A., Ong, B. T., Hoi, K. M., Teo, G., Lu, M. Y., & Wang, D. I. C. (2010) · Analytical Biochemistry · doi:10.1016/j.ab.2010.07.029 · Cited by 38 · see citing works
Self-citationGlycoengineering Chinese hamster ovary cells: a short history
Donini, R., Haslam, S. M., & Kontoravdi, C. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200840 · Cited by 37 · see citing works
Sialylation enhancement of CTLA4‐Ig fusion protein in Chinese hamster ovary cells by dexamethasone
Jing, Y., Qian, Y., & Li, Z. J. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22827 · Cited by 35 · see citing works
Glycoengineering of Mammalian Expression Systems on a Cellular Level
Heffner, K. M., Wang, Q., Hızal, D. B., Can, Ö., & Betenbaugh, M. J. (2018) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2017_57 · Cited by 34 · see citing works
RNA interference technology to improve recombinant protein production in Chinese hamster ovary cells
Wu, S. (2009) · Biotechnology Advances · doi:10.1016/j.biotechadv.2009.03.002 · Cited by 33 · see citing works
Current state and perspectives on erythropoietin production
Lee, J. S., Ha, T. K., Lee, S. J., & Lee, G. M. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-4291-x · Cited by 31 · see citing works
Park, J. H., Wang, Z., Jeong, H., Park, H. H., Kim, B., Tan, W., Choi, S. S., & Park, T. H. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-4203-0 · Cited by 31 · see citing works
Pereira, A. G. M., Templeton, N., & Young, J. D. (2014) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.13.65 · Cited by 30 · see citing works
Applying the science of measurement to biology: Why bother?
Coxon, C. H., Longstaff, C., & Burns, C. J. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000338 · Cited by 30 · see citing works
Ha, T. K., Hansen, A. H., Kildegaard, H. F., & Lee, G. M. (2019) · Metabolic Engineering · doi:10.1016/j.ymben.2019.11.008 · Cited by 29 · see citing works
Eisenhut, P., Marx, N., Borsi, G., Papež, M., Ruggeri, C., Baumann, M., & Borth, N. (2023) · New Biotechnology · doi:10.1016/j.nbt.2023.11.003 · Cited by 32 · see citing works
Glycobiomimics and glycobiosensors
Gerlach, J. Q., Cunningham, S., Kane, M., & Joshi, L. (2010) · Biochemical Society Transactions · doi:10.1042/bst0381333 · Cited by 27 · see citing works
N-Glycosylation Modification of Plant-Derived Virus-Like Particles: An Application in Vaccines
Kim, H.-S., Jeon, J., Lee, K., & Ko, K. (2014) · BioMed Research International · doi:10.1155/2014/249519 · Cited by 31 · see citing works
Geisler, C., & Jarvis, D. L. (2012) · Metabolic Engineering · doi:10.1016/j.ymben.2012.08.005 · Cited by 26 · see citing works
RNA interference of cofilin in Chinese hamster ovary cells improves recombinant protein productivity
Hammond, S., & Lee, K. H. (2011) · Biotechnology and Bioengineering · doi:10.1002/bit.23322 · Cited by 23 · see citing works
Strategies for Engineering Protein N-Glycosylation Pathways in Mammalian Cells
Wang, Q., Stuczynski, M. C., Gao, Y., & Betenbaugh, M. J. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2760-9_20 · Cited by 23 · see citing works
CRISPR‐interceded CHO cell line development approaches
Amiri, S., Adibzadeh, S., Ghanbari, S., Rahmani, B., Kheirandish, M. H., Farokhi‐Fard, A., Dastjerdeh, M. S., & Davami, F. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28329 · Cited by 21 · see citing works
Škulj, M., Pezdirec, D., Gaser, D., Kreft, M., & Zorec, R. (2014) · BMC Biotechnology · doi:10.1186/1472-6750-14-76 · Cited by 21 · see citing works
Rapid Identification of Terminal Sialic Acid Linkage Isomers by Pseudo‐MS3 Mass Spectrometry
Chen, C., Lin, Y., Lin, J., Li, S., Ren, C., Wu, C., & Chen, C. (2015) · Israel Journal of Chemistry · doi:10.1002/ijch.201400141 · Cited by 21 · see citing works
Production of Highly Sialylated Monoclonal Antibodies
(2012) · InTech eBooks · doi:10.5772/51301 · Cited by 20 · see citing works
Chen, F., Li, F., Wang, J., Zhou, Y., Ye, Z., Zhao, L., & Tan, W. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3484-z · Cited by 20 · see citing works
Hebert, C. G., Valdés, J. J., & Bentley, W. E. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22411 · Cited by 19 · see citing works
Downstream Processing for Biopharmaceuticals Recovery
Mehta, A. (2019) · Environmental chemistry for a sustainable world · doi:10.1007/978-3-030-01881-8_6 · Cited by 18 · see citing works
Cha, H.-M., Lim, J.-H., Yeon, J.-H., Hwang, J.-M., & Kim, D. (2017) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2017.04.010 · Cited by 17 · see citing works
Lee, J. H., Kim, Y., & Lee, G. M. (2015) · Biotechnology Progress · doi:10.1002/btpr.2115 · Cited by 17 · see citing works
Noncoding RNAs, post-transcriptional RNA operons and Chinese hamster ovary cells
Stiefel, F., Fischer, S., Hackl, M., Handrick, R., Hesse, F., Borth, N., Otte, K., & Grillari, J. (2015) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.14.65 · Cited by 15 · see citing works
Dorokhov, Y. L., Sheshukova, E. V., Kosobokova, E. N., Shindyapina, A. V., Kosorukov, V. S., & Komarova, T. V. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916080058 · Cited by 15 · see citing works
Kwak, C. Y., Park, S., Lee, C.-G., Okino, N., Ito, M., & Kim, J. H. (2017) · Scientific Reports · doi:10.1038/s41598-017-13609-4 · Cited by 15 · see citing works
Sam, N. T., Misaki, R., Ohashi, T., & Fujiyama, K. (2018) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2018.01.010 · Cited by 12 · see citing works
Sello, G., Bernasconi, S., Orsini, F., Paolo, M., Gennaro, P. D., & Bestetti, G. (2007) · Journal of Molecular Catalysis B Enzymatic · doi:10.1016/j.molcatb.2007.10.014 · Cited by 11 · see citing works
Insights into the loss of protein sialylation in an fc-fusion protein-producing CHO cell bioprocess
Chen, X., Liu, X., Xiao, Z., Liu, J., Zhao, L., Tan, W., & Fan, L. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-09850-8 · Cited by 9 · see citing works
CZE for glycoform profiling and quality assessment of recombinant human interleukin‐7
Alahmad, Y., Tran, N. T., Duboeuf, J., Grégoire, A., Rancé, I., & Taverna, M. (2009) · Electrophoresis · doi:10.1002/elps.200800789 · Cited by 9 · see citing works
CHO Cell Engineering for Improved Process Performance and Product Quality
Fischer, S., & Otte, K. (2019) · doi:10.1002/9783527811410.ch9 · Cited by 9 · see citing works
Lim, J.-H., Kim, J., Cha, H.-M., Kang, S.-H., Han, H., Ji, M., Cheon, S., Kang, M., Kim, H. H., & Kim, D. (2022) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2022.110007 · Cited by 8 · see citing works
Metabolic engineering of CHO cells to prepare glycoproteins
Wang, Q., & Betenbaugh, M. J. (2018) · Emerging Topics in Life Sciences · doi:10.1042/etls20180056 · Cited by 7 · see citing works
Application of Genetic Engineering in Biotherapeutics Development
Schweickert, P. G., & Cheng, Z. (2019) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-019-09411-6 · Cited by 7 · see citing works
Plant-Produced Biopharmaceuticals
Gerlach, J. Q., Kilcoyne, M., McKeown, P. C., Spillane, C., & Joshi, L. (2010) · Springer eBooks · doi:10.1007/978-3-642-04812-8_7 · Cited by 6 · see citing works
Qian, Y., Lewis, A. M., Sidnam, S. M., Bergeron, A. A., Abu‐Absi, N. R., Vaidyanathan, N., Deresienski, A., Qian, N., Borys, M., & Li, Z. J. (2016) · Process Biochemistry · doi:10.1016/j.procbio.2016.11.018 · Cited by 6 · see citing works
Chen, X., Liu, J., Liu, X., Li, F., Zhao, L., & Tan, W. (2018) · Process Biochemistry · doi:10.1016/j.procbio.2018.08.015 · Cited by 6 · see citing works
A high‐throughput capillary isoelectric focusing immunoassay for fingerprinting protein sialylation
Markely, L. R. A., Cheung, L., Choi, Y. J., Ryll, T., Estes, S. D., Prajapati, S., Turyan, I., Frenkel, R., Sosic, Z., Lambropoulos, J., et al. (2015) · Biotechnology Progress · doi:10.1002/btpr.2206 · Cited by 5 · see citing works
Evaluating the impact of suramin additive on CHO cells producing Fc-fusion protein
Lim, J.-H., Cha, H.-M., Han, H., & Kim, D. (2019) · Biotechnology Letters · doi:10.1007/s10529-019-02728-9 · Cited by 5 · see citing works
Enhancement of sialylation in rIgG in glyco-engineered Chinese hamster ovary cells
Nguyen, T. S., Misaki, R., Ohashi, T., & Fujiyama, K. (2020) · Cytotechnology · doi:10.1007/s10616-020-00381-z · Cited by 5 · see citing works
Improving sialylation of recombinant biologics for enhanced therapeutic efficacy
Chan, K. F., Goh, J. S., & Song, Z. (2014) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.14.44 · Cited by 4 · see citing works
Improvement in accuracy and specificity of high-throughput sialic acid assay
Markely, L. R. A., Jonnalagadda, K. N., Sinacore, M. S., Ryll, T., & Prajapati, S. (2012) · Analytical Methods · doi:10.1039/c2ay25448d · Cited by 4 · see citing works
Markely, L. R. A., Kurt, L., Lau, J., Mane, S., Guan, B., Ryll, T., Estes, S. D., Prajapati, S., Bakhshayeshi, M., & Pieracci, J. P. (2014) · Biotechnology Progress · doi:10.1002/btpr.1873 · Cited by 4 · see citing works
Rapid Antibody Glycoengineering in CHO Cells Via RNA Interference and CGE-LIF N-Glycomics
Kotidis, P., Marbiah, M. M., Donini, R., Gómez, I. A., del Val, I. J., Haslam, S. M., Polizzi, K. M., & Kontoravdi, C. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1685-7_7 · Cited by 4 · see citing works
Optimizing Chinese hamster ovary cell line development via targeted control of N-glycosylation
Alves, C. S., & Prajapati, S. (2015) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.15.25 · Cited by 4 · see citing works
Computational analysis reveals non-consensus N-glycosylation sequons in antibody Fab region
Qiu, B., Chen, E., Flick, T. G., & Letarte, S. (2025) · mAbs · doi:10.1080/19420862.2025.2574406 · Cited by 3 · see citing works
Alkanaimsh, S., AlSalal, A. M., & El-Touney, H. (2024) · Processes · doi:10.3390/pr12050979 · Cited by 3 · see citing works
Liu, J., Chen, X., Li, F., Deng, X., Poon, H. F., Tan, W., & Liu, X. (2015) · Biotechnology Letters · doi:10.1007/s10529-015-1815-3 · Cited by 3 · see citing works
High‐throughput analysis of intraclonal variability of glycoprotein sialylation
Markely, L. R. A., & Wang, D. I. C. (2011) · Biotechnology Progress · doi:10.1002/btpr.738 · Cited by 3 · see citing works
Self-citationLuo, C., Chen, S., Xu, N., Sai, W., Zhao, W., Li, Y. C., Hu, X. J., Tian, H., Gao, X. D., & Yao, W. B. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.085 · Cited by 2 · see citing works
Lim, J.-H., Cha, H.-M., Park, H., Kim, H. H., & Kim, D. (2017) · KSBB Journal · doi:10.7841/ksbbj.2017.32.3.193 · Cited by 2 · see citing works
Han, H., Lim, J.-H., Cha, H.-M., Lee, J.-H., & Kim, D. (2021) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-020-0125-3 · Cited by 1 · see citing works
Piao, Y., Yun, S. Y., Kim, H. S., Park, B. K., Ha, H. C., Fu, Z., Jang, J. M., Back, M. J., Shin, I. C., Won, J. H., et al. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2022.071 · Cited by 1 · see citing works
High-throughput quantification of glycoprotein sialylation
Markely, L. R. A. (2011) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 1 · see citing works
Emerging Alternative Production Systems
Jostock, T. (2007) · doi:10.1002/9783527619740.ch19 · Cited by 1 · see citing works
Emerging Alternative Production Systems
Sommer, B., Laux, H., Frenzel, A., & Jostock, T. (2014) · doi:10.1002/9783527682423.ch21 · Cited by 1 · see citing works
Hebert, C. G. (2008) · University Libraries (University of Maryland)
The Role of Neu1 Sialidase in Toll-Like Receptor Activation
Amith, S. R. (2009) · QSpace (Queen's University Library)
Towards the cell-free expression of glycoproteins
Exley, K. (2017) · Spiral (Imperial College London) · doi:10.25560/68742
Santoso, A., Septisetyani, E. P., Ramadani, R. D., Rubiyana, Y., Prasetyaningrum, P. W., Wisnuwardhani, P. H., Kusumawati, A., & Nuraini, N. (2022) · HAYATI Journal of Biosciences · doi:10.4308/hjb.29.2.204-213
Glycosylation control strategies for recombinant therapeutic proteins in CHO cells
Wang, W., Li, W., Wang, Q., Li, X., Wang, T., & Zhang, J. (2026) · Biochimie · doi:10.1016/j.biochi.2026.02.020
Mise en oeuvre de dosages pour le diagnostic précoce de l'hypothyroïdie
Iss, C. (2015) · theses.fr (ABES) · doi:10.70675/f9f2aeebza5a8z4cf3zb9afzd52e7504b286
Glycosylation in Quality and Safety of Therapeutic Proteins
Matsumoto, Y., Kim, J., McKenna, K. R., Biel, T. G., Kirshner, S., Falkowski, V. M., & Ju, T. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100163
- Authors
- Ngantung, F. A., Miller, P. G., Brushett, F. R., Tang, G. L., & Wang, D. I. C.
- Affiliations
- Massachusetts Institute of Technology (US)
- University of Pennsylvania (US)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Wang, Daniel I.C.
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2006-05-03
- Volume
- 95
- Issue
- 1
- Pages
- 106-119
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- OpenAlex
- W2052231275
- Cited by
- 97
- References
- 51
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 1 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 4 · 2012: 5
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- neuraminidase, RNA interference, siRNA, sialic acid, glycoprotein sialylation, desialylation, recombinant protein expression, CHO cells, interferon-gamma, asialoglycoprotein receptor, stable cell lines, glycosidase inhibition
- MeSH terms
- Animals, Cricetulus, Glycoproteins, Cricetinae, Neuraminidase, Protein Engineering, CHO Cells, N-Acetylneuraminic Acid, Genetic Enhancement, RNA Interference
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
