Virus stalls Genzyme plant
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Plant‐made vaccines for humans and animals
Rybicki, E. P. (2010) · Plant Biotechnology Journal · doi:10.1111/j.1467-7652.2010.00507.x · Cited by 336 · see citing works
“A later report (Bethencourt, 2009) states that ‘The US Food and Drug Administration (FDA) has contacted rival manufacturers Shire of Basingstoke, UK, and Carmiel, Israel-based Protalix, who have enzyme replacement therapies for Gaucher disease in clinical trials, to file treatment protocols, which…”
BackgroundViral contamination in biologic manufacture and implications for emerging therapies
Barone, P. W., Wiebe, M. E., Leung, J. C., Hussein, I. T. M., Keumurian, F. J., Bouressa, J., Brussel, A., Chen, D., Chong, M., Dehghani, H., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0507-2 · Cited by 212 · see citing works
Plants as sources of natural and recombinant anti-cancer agents
Buyel, J. F. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.02.002 · Cited by 205 · see citing works
Sense codon reassignment enables viral resistance and encoded polymer synthesis
Robertson, W. E., Funke, L. F. H., de la Torre, D., Fredens, J., Elliott, T. S., Spinck, M., Christova, Y., Cervettini, D., Böge, F. L., Liu, K. C., et al. (2021) · Science · doi:10.1126/science.abg3029 · Cited by 192 · see citing works
Buyel, J. F. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2018.01893 · Cited by 174 · see citing works
“Utilizing these side streams has a low risk because biomass from wild type as well as transgenic plants tends not to contain human pathogens, whereas the waste streams from mammalian cell cultures may contain infectious adventitious viruses (Jennings, 1998; Merten, 2002; Bethencourt, 2009).”
BackgroundYin, G., Garces, E. D., Yang, J., Zhang, J., Tran, C., Steiner, A. R., Roos, C. M., Bajad, S. U., Hudak, S. A., Penta, K., et al. (2012) · mAbs · doi:10.4161/mabs.4.2.19202 · Cited by 145 · see citing works
“The antibodies are produced with high fidelity (<10 missense errors/ codon; unpublished results), are fully soluble, non-aggregated, correctly folded, functional in biochemical and cell-based assays, and are free of inherent biological contamination such as viruses.(36) The open nature of the system allows us to profi…”
BackgroundKizhner, T. A., Azulay, Y., Hainrichson, M., Tekoah, Y., Arvatz, G., Shulman, A., Ruderfer, I., Aviezer, D., & Shaaltiel, Y. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.08.002 · Cited by 130 · see citing works
Removal of xenotropic murine leukemia virus by nanocellulose based filter paper
Asper, M., Hanrieder, T., Quellmalz, A., & Mihranyan, A. (2015) · Biologicals · doi:10.1016/j.biologicals.2015.08.001 · Cited by 84 · see citing works
“The virus contamination incident at the Genzyme factory, Massachusetts, in 2009 testifies to the scale of the problem [1].”
BackgroundEnvironmental Impacts of Cultured Meat: A Cradle-to-Gate Life Cycle Assessment
Risner, D., Negulescu, P. G., Kim, Y., Nguyen, C., Siegel, J. B., & Spang, E. S. (2024) · ACS Food Science & Technology · doi:10.1021/acsfoodscitech.4c00281 · Cited by 88 · see citing works
Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications
Gustafsson, S., Lordat, P., Hanrieder, T., Asper, M., Schaefer, O., & Mihranyan, A. (2016) · Materials Horizons · doi:10.1039/c6mh00090h · Cited by 63 · see citing works
Viral clearance for biopharmaceutical downstream processes
Shukla, A. A., & Aranha, H. (2015) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.14.62 · Cited by 63 · see citing works
Marets, N., Kuo, D., Torrey, J. R., et al. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700252 · Cited by 61 · see citing works
Marcus-Sekura, C. J., Richardson, J. C., Harston, R. K., Sane, N., & Sheets, R. (2011) · Biologicals · doi:10.1016/j.biologicals.2011.08.003 · Cited by 55 · see citing works
Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements
Ma, N. J., & Isaacs, F. J. (2016) · Cell Systems · doi:10.1016/j.cels.2016.06.009 · Cited by 55 · see citing works
“For example, biological-based production suffers losses from viral infection (Calendar, 2006), such as the 2009 infection of Genzyme’s bioreactors that caused $300 million in losses of high-value therapeutics and alleged loss of human life (Bethencourt, 2009).”
Overcoming Challenges in Engineering the Genetic Code
Lajoie, M. J., Söll, D. G., & Church, G. M. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.09.003 · Cited by 52 · see citing works
“This would prevent viruses from hijacking their translation machinery (potentially saving hundreds of millions of dollars from lost productivity [36,37]) and would thwart transfer of functional genetic information with natural organisms [13].”
Gengenbach, B. B., Keil, L., Opdensteinen, P., Müschen, C. R., Melmer, G., Lentzen, H., Bührmann, J., & Buyel, J. F. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.27076 · Cited by 50 · see citing works
“The last two aspects are particularly important when comparing plants to mammalian cells because disastrous contamination with human pathogens is unlikely in plants (Bethencourt, 2009; Zimran et al., 2011) and the manufacturing capacity can be rapidly adapted to market demands.”
Buyel, J. F., & Fischer, R. (2015) · Process Biochemistry · doi:10.1016/j.procbio.2015.02.017 · Cited by 38 · see citing works
Gagnieur, L., Cheval, J., Gratigny, M., Hébert, C., Muth, E., Dumarest, M., & Éloit, M. (2014) · Biologicals · doi:10.1016/j.biologicals.2014.02.002 · Cited by 38 · see citing works
“FBS was the likely source of infection of fermenters by the Cache Valley Virus (CVV) [1], a Vesivirus [2], and reoviruses [3].”
MethodKuo, D., Liu, M., Kumar, K. R. S., et al. (2020) · Small · doi:10.1002/smll.202001721 · Cited by 36 · see citing works
Kohman, R. E., Kunjapur, A. M., Hysolli, E., Wang, Y., & Church, G. M. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201707976 · Cited by 33 · see citing works
CRISPR Technologies in Chinese Hamster Ovary Cell Line Engineering
Glinšek, K., Bozovičar, K., & Bratkovič, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098144 · Cited by 35 · see citing works
Ma, D., Li, H., Meng, Z., Zhang, C., Zhou, J., Xia, J., & Wang, Y. (2021) · Environmental Science & Technology · doi:10.1021/acs.est.1c04644 · Cited by 27 · see citing works
Combating viral contaminants in CHO cells by engineering innate immunity
Chiang, A. W. T., Li, S., Kellman, B. P., Chattopadhyay, G., Zhang, Y., Kuo, C., Gutierrez, J. M., Ghazi, F., Schmeisser, H., Ménard, P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45126-x · Cited by 21 · see citing works
History and Promise of Plant-Made Vaccines for Animals
Rybicki, E. P. (2018) · Springer eBooks · doi:10.1007/978-3-319-90137-4_1 · Cited by 21 · see citing works
“A contamination of Genzyme’s mammalian cell production facilities in 2009 with a mammalian calicivirus led to the FDA allowing Protalix to supply the drug to patients who needed it, and to accelerated licensure (Bethencourt 2009).”
BackgroundManukyan, L., Padova, J., & Mihranyan, A. (2019) · Biologicals · doi:10.1016/j.biologicals.2019.03.001 · Cited by 18 · see citing works
Feroz, H., Chennamsetty, N., Byers, S., Holstein, M., Li, Z.-J., & Ghose, S. (2022) · Biotechnology and Bioengineering · doi:10.1002/bit.28034 · Cited by 12 · see citing works
“All mammalian manufacturing processes need to effectively remove potential contaminants, such as viruses, other impurities, and product degradants, to maintain drug efficacy, while ensuring patients safety (Bethencourt, 2009; Pastoret, 2010) and compliance with regulatory”
BackgroundBioreactor-Based Production of Glycoproteins in Plant Cell Suspension Cultures
Holland, T., & Buyel, J. F. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7312-5_11 · Cited by 14 · see citing works
Detection of Adventitious Agents Using Next-Generation Sequencing
Richards, B., Cao, S., Plavsic, M., Pomponio, R. J., Davies, C., Mattaliano, R. J., Madden, S. F., Klinger, K., & Palermo, A. (2014) · PDA Journal of Pharmaceutical Science and Technology · doi:10.5731/pdajpst.2014.01025 · Cited by 14 · see citing works
“In 2008 and 2009, Genzyme bioreactors producing biopharmaceuticals in Chinese hamster ovary (CHO) cells were contaminated with calicivirus 2117 (also called vesivirus 2117), resulting in a temporary shutdown of a manufacturing facility, limited drug supplies for patients, and lost revenues (1).”
BackgroundMacDonald, M. L., Polson, S. W., & Lee, K. H. (2021) · mSphere · doi:10.1128/msphere.01336-20 · Cited by 11 · see citing works
“tamination events involved Cache Valley virus (4), vesivirus 2117 (5), reovirus (4), and epi-”
BackgroundDevelopment of a cell surface display system in Chlamydomonas reinhardtii
Molino, J. V. D., Carpine, R., Gademann, K., Mayfield, S. P., & Sieber, S. (2021) · Algal Research · doi:10.1016/j.algal.2021.102570 · Cited by 11 · see citing works
Feroz, H., Cetnar, D. P., Hewlett, R., Sharma, S., Holstein, M., Ghose, S., & Li, Z.-J. (2021) · Biotechnology Journal · doi:10.1002/biot.202100176 · Cited by 9 · see citing works
“[3] Viral clearance (VC) validation studies are critical for FDA (Food and Drug Administration) approval of any IND (Investigational NewDrug) or BLA (Biologics License Application) filings and are typically conducted at third party testing sites to demonstrate robust VC for safe administration of therapeutics to patie…”
BackgroundDjemal, L., Fournier, C., von Hagen, J., et al. (2020) · Biotechnology Progress · doi:10.1002/btpr.3117 · Cited by 8 · see citing works
Risk Mitigation in Preventing Adventitious Agent Contamination of Mammalian Cell Cultures
Shiratori, M., & Kiss, R. (2017) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2017_38 · Cited by 6 · see citing works
Vom Design der Moleküle des Lebens zum Design von Leben: Zukünftige Anwendungen von DNA‐Technologien
Kohman, R. E., Kunjapur, A. M., Hysolli, E., Wang, Y., & Church, G. M. (2018) · Angewandte Chemie · doi:10.1002/ange.201707976 · Cited by 6 · see citing works
Toward the commercialization of recombinant pharmaceuticals expressed in plants
Washida, H., Yoshinaka, K., Yamada, O., Ookawa, S., & Yuki, M. (2025) · Plant Biotechnology · doi:10.5511/plantbiotechnology.24.1130a · Cited by 4 · see citing works
Bioprocess Engineering of Plant Cell Suspension Cultures
Andrews, G. R., & Roberts, S. C. (2017) · doi:10.1002/9783527800599.ch10 · Cited by 5 · see citing works
How Plants Can Contribute to the Supply of Anticancer Compounds
Buyel, J. F. (2017) · Springer eBooks · doi:10.1007/978-3-319-53880-8_2 · Cited by 4 · see citing works
“The last two aspects are particularly important when comparing plants to mammalian cells because disastrous contamination with human pathogens is unlikely (Bethencourt 2009; Zimran et al.”
BackgroundSeem, K., & Kaur, S. (2023) · doi:10.1002/9781119875116.ch18 · Cited by 3 · see citing works
Viral safety testing for biopharmaceuticals: Current and future prospects
Yusa, K., Yuzhe, Y. U. S. A., & Uchida, K. (2020) · Translational and Regulatory Sciences · doi:10.33611/trs.2020-017 · Cited by 2 · see citing works
“Viral contamination occurring in the bioreactor lead to serious consequences for patients and manufacturers, including the complete shutdown of manufacturing facilities, leading to severe drug shortages and consequent financial losses [2, 3].”
BackgroundGemmell, D. K., Mack, A. A., Wegmann, S., Han, D., Tuccelli, R., Johnson, M., & Miller, C. (2021) · Engineering in Life Sciences · doi:10.1002/elsc.202100044 · Cited by 1 · see citing works
“In severe cases, contamination events can create drug shortages that affect patient quality of life [5,7,8] additionally, competitors could profit from accelerated drug approval processes [5,9,10].”
BackgroundQuality of biopharmaceuticals: Comparability exercise and post-approval surveillance
Alsamil, A. M. (2022) · doi:10.33540/1484 · Cited by 2 · see citing works
Genetic Code-Locking Confers Stable Virus Resistance to a Recoded Organism
Zürcher, J. F., Dickson, A., Kappes, T., Kleefeldt, A. A., Liu, K. C., Salmond, G. P. C., & Chin, J. W. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00075 · Cited by 1 · see citing works
Анатольевна, Е. М., Mukhamedzhanova, A., Mahmud, R. S., Khammadov, N. I., Валерьевич, У. К., Nesterova, I. A., Фаизов, Т. Х., & Ilinskaya, O. N. (2021) · BioNanoScience · doi:10.1007/s12668-021-00862-1 · Cited by 1 · see citing works
Григорьевич, Ю. С., Zhivoderov, S. P., Koltsov, A., et al. (2021) · Biotekhnologiya · doi:10.21519/0234-2758-2021-37-1-69-80 · Cited by 1 · see citing works
Raw Materials in the Manufacture of Biotechnology Products
Cordoba-Rodriguez, R. (2011) · Elsevier eBooks · doi:10.1016/b978-0-08-088504-9.00232-4
N-GLYCOSYLATION AND GLYCOENGINEERING IN THE MUSHROOM FORMING FUNGUS SCHIZOPHYLLUM COMMUNE
Berends, E. (2013) · Utrecht University Repository (Utrecht University)
Optimisation de la production de protéines recombinantes avec des cellules de tabac en suspension
Boivin, E. B. (2010) · PolyPublie (École Polytechnique de Montréal)
Raw Materials in the Manufacture of Biotechnology Products
Cordoba-Rodriguez, R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-444-64046-8.00179-8
Sato, K., Yumioka, H., Isoyama, J., Dohi, K., Yamanaka, A., Ohashi, T., Misaki, R., & Fujiyama, K. (2023) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2023.05.009
Wieser, A., Modrof, J., & Kreil, T. R. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28473
“The downtime can lead to unmet patient needs, dramatic economic consequences, and severe impact on the reputation of an affected company (Bethencourt, 2009).”
BackgroundHsu, T. Y., Talley, M. J., Yang, P., Geiselhoeringer, A., Yang, C. L.-H., Gorla, A., Rahman, M. J., Silva, L., Chen, D., & Yang, B. (2024) · Biotechnology Progress · doi:10.1002/btpr.3485
- Authors
- Bethencourt, V.
- Corresponding author
- Bethencourt, Victor
- Venue
- Nature Biotechnology
- Published
- 2009-08
- Volume
- 27
- Issue
- 8
- Pages
- 681-681
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W1985218277
- Cited by
- 51
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 1
- Type
- other
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Keywords
- Genzyme, Myozyme, Gaucher disease, Fabry disease, enzyme replacement therapy, CHO cells, supply constraints, lost revenue, miglustat
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