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Development of a Serum-Free Media Based on the Optimal Combination of Recombinant Protein Additives and Hydrolysates of Non-animal Origin to Produce Immunoglobulins

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Abstract

The potential ability to cultivate a recombinant immunoglobulin (IgG1)-producer line in Iscove’s Modified Dulbecco Medium (IMDM) as the base cultivation medium with the introduction of recombinant proteins and hydrolysates of non-animal origin was studied. Recombinant insulin, human serum albumin (produced by E. coli bacteria), and transferrin (by Pichia pastoris yeasts) were used to enrich the medium. A combination of protein additives (part of the developed medium) allowed an increase in the productivity of a stable producer culture of recombinant humanized antibodies based on CHO-line cells by 44% as compared with the used complex commercial insulin–transferrin–selenium (ITS) additive. The introduction of pea and rice protein hydrolysates containing peptides with a molecular weight lower than 5 kDa to modified IMDM medium contributed to an increase in line productivity by 3.9 and 4.5 times, respectively.

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REFERENCES

  1. Jayapal, K.P., Wlaschin, K.F., Hu, W., and Yap, M.G., Chem. Eng. Prog., 2007, vol. 103, no. 10, pp. 40–47.

    CAS  Google Scholar 

  2. Wurm, F.M., Nat. Biotechnol., 2004, vol. 22, no. 11, pp. 1393–1398.

    Article  CAS  Google Scholar 

  3. Ryu, J.H., Kim, M.S., Lee, G.M., Choi, C.Y., and Kim, B.S., Biomaterials, 2005, vol. 26, no. 14, pp. 2173–2181.

    Article  CAS  Google Scholar 

  4. Yoon, S.K., Hong, J.K., Choo, S.H., Song, J.Y., Park, H.W., and Lee, G.M., J. Biotechnol., 2006, vol. 122, no. 4, pp. 463–472.

    Article  CAS  Google Scholar 

  5. Fox, S.R., Patel, U.A., Yap, M.G., and Wang, D.I., Biotechnol. Bioeng., 2004, vol. 85, no. 2, pp. 177–184.

    Article  CAS  Google Scholar 

  6. Kim, D.Y., Lee, J.C., Chang, H.N., and Oh, D.J., Cytotechnology, 2005, vol. 47, nos. 1–3, pp. 37–49.

    Article  CAS  Google Scholar 

  7. Nienow, A.W., Cytotechnology, 2006, vol. 50, nos. 1–3, pp. 9–33.

    Article  CAS  Google Scholar 

  8. Arden, N. and Betenbaugh, M.J., Cytotechnology, 2006, vol. 50, nos. 1–3, pp. 77–92.

    Article  CAS  Google Scholar 

  9. Liu, C.H. and Chen, L.H., Cytotechnology, 2007, vol. 54, no. 2, pp. 89–96.

    Article  CAS  Google Scholar 

  10. Borys, M.C., Linzer, D.I., and Papoutsakis, E.T., Biotechnology (N.Y.), 1993, vol. 11, no. 6, pp. 720–724.

    CAS  Google Scholar 

  11. Ozturk, S.S. and Palsson, B.O., Biotechnol. Prog., 1991, vol. 7, no. 6, pp. 481–494.

    Article  CAS  Google Scholar 

  12. Lin, A.A., Kimura, R., and Miller, W.M., Biotechnol. Bioeng., 1993, vol. 42, no. 3, pp. 339–350.

    Article  CAS  Google Scholar 

  13. Furukawa, K. and Ohsuye, K., Cytotechnology, 1998, vol. 26, no. 2, pp. 153–164.

    Article  CAS  Google Scholar 

  14. Barnes, D. and Sato, G., Cell, 1980, vol. 22, no. 3, pp. 649–655.

    Article  CAS  Google Scholar 

  15. Darfler, F.J., In Vitro Cell. Dev. Biol., 1990, vol. 26, no. 8, pp. 769–778.

    Article  CAS  Google Scholar 

  16. Kan, M. and Yamane, I., J. Cell Physiol., 1982, vol. 111, no. 2, pp. 155–162.

    Article  CAS  Google Scholar 

  17. Guilbert, L.J. and Iscove, N.N., Nature, 1976, vol. 263, no. 5578, pp. 594–595.

    Article  CAS  Google Scholar 

  18. Lambert, K. and Birch, J., Anim. Cell Biotechnol., 1985, vol. 1, pp. 85–122.

    Google Scholar 

  19. Kawamoto, T., Sato, J.D., Le, A., McClure, D.B., and Sato, G.H., Anal. Biochem., 1983, vol. 130, no. 2, pp. 445–453.

    Article  CAS  Google Scholar 

  20. Kovár, J., Folia Biol., 1987, vol. 33, no. 6, pp. 377–384.

    Google Scholar 

  21. Bretscher, M.S., Sci. Am., 1985, vol. 253, no. 4, pp. 100–108.

    Article  CAS  Google Scholar 

  22. Trowbridge, I.S. and Omary, M.B., Proc. Natl. Acad. Sci. U. S. A., 1981, vol. 78, no. 5, pp. 3039–3043.

    Article  CAS  Google Scholar 

  23. Iscove, N.N. and Melchers, F., J. Exp. Med., 1978, vol. 147, no. 3, pp. 923–933.

    Article  CAS  Google Scholar 

  24. Baré, G., Charlier, H., De Nijs, L., Verhoeye, F., Schneider, Y.-J., Agathos, S., and Thonart, P., in 17th ESACT Meeting Tylösand, Lindner-Olsson, E., Chatzissavidou, N., and Lüllau, E., Netherlands, Dordrecht: Springer-Science+ Business Media, B.V., 2001, pp. 217–219.

  25. Mols, J., Peeters-Joris, C., Agathos, S.N., and Schneider, Y.J., Biotechnol. Lett., 2004, vol. 26, no. 13, pp. 1043–1046.

    Article  CAS  Google Scholar 

  26. Mosser, M., Chevalot, I., Olmos, E., Blanchard, F., Kapel, R., Oriol, E., Marc, I., and Marc, A., Cytotechnology, 2013, vol. 65, no. 4, pp. 629–641.

    Article  CAS  Google Scholar 

  27. Richardson, J., Shah, B., Bondarenko, P.V., Bhebe, P., Zhang, Z., Nicklaus, M., and Kombe, M.C., Biotechnol. Prog., 2015, vol. 31, no. 2, pp. 522–531.

    Article  CAS  Google Scholar 

  28. Gupta, A.J., Gruppen, H., Maes, D., Boots, J.W., and Wierenga, P.A., J. Agric. Food Chem., 2013, vol. 61, no. 45, pp. 10613–10625.

    Article  CAS  Google Scholar 

  29. Donaldson, M.S. and Shuler, M.L., Biotechnol. Prog., 1998, vol. 14, no. 4, pp. 573–579.

    Article  CAS  Google Scholar 

  30. Franěk, F., Hohenwarter, O., and Katinger, H., Biotechnol. Prog., 2000, vol. 16, no. 5, pp. 688–692.

    Article  Google Scholar 

  31. Heidemann, R., Zhang, C., Qi, H., Larrick, RuleJ., Rozales, C., Park, S., Chuppa, S., Ray, M., Michaels, J., Konstantinov, K., and Naveh, D., Cytotechnology, 2000, vol. 32, no. 2, pp. 157–167.

    Article  CAS  Google Scholar 

  32. Sung, Y.H., Lim, S.W., Chung, J.Y., and Lee, G.M., Appl. Microbiol. Biotechnol., 2004, vol. 63, no. 5, pp. 527–536.

    Article  CAS  Google Scholar 

  33. Bobik, T.V., Popov, R.Y., Aliev, T.K., Mokrushina, Y.A., Shamborant, O.G., Khurs, E.N., Knorre, V.D., Smirnov, I.V., and Gabibov, A.G., Bull. Exp. Biol. Med., 2019, vol. 167, no. 3, pp. 335–338.

    Article  CAS  Google Scholar 

  34. Mizutani, K., Hashimoto, K., Takahashi, N., Hirose, M., Aibara, S., and Mikami, B., Biosci. Biotechnol. Biochem., 2010, vol. 74, no. 2, pp. 309–315.

    Article  CAS  Google Scholar 

  35. Laemmli, U.K., Nature, 1970, vol. 227, no. 5259, pp. 680–685.

    Article  CAS  Google Scholar 

  36. Gusarova, V., Vorobjeva, T., Gusarov, D., Lasman, V., and Bayramashvili, D., J. Chromatogr., A, 2007, vol. 1176, nos. 1–2, pp. 157–162.

    Article  CAS  Google Scholar 

  37. Gusarov, D., Nekipelova, V., Gusarova, V., Lasman, V., and Bairamashvili, D., J. Chromatogr. B, 2009, vol. 877, nos. 11–12, pp. 1216–1220.

    Article  CAS  Google Scholar 

  38. Bobik, T.V., Vorob’ev, I.I., Ponomarenko, N.A., Gabibov, A.G., and Miroshnikov, A.I., Russ. J. Bioorg. Chem., 2008, vol. 34, no. 1, pp. 49–55.

    Article  CAS  Google Scholar 

  39. Wu, S. and Letchworth, G.J., BioTechniques, 2004, vol. 36, no. 1, pp. 152–154.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement no. 075-15-2019-1391 on June 19, 2019, unique identifier of the project RFMEFI60717X0177).

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Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    D. S. Balabashin, E. N. Kaliberda, I. V. Smirnov, Y. A. Mokrushina, T. V. Bobik, T. K. Aliev, D. A. Dolgikh & M. P. Kirpichnikov

  2. Chemistry Department, Moscow State University, 119991, Moscow, Russia

    T. K. Aliev

  3. Biology Department, Moscow State University, 119991, Moscow, Russia

    D. A. Dolgikh & M. P. Kirpichnikov

Authors
  1. D. S. Balabashin
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  2. E. N. Kaliberda
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  3. I. V. Smirnov
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  4. Y. A. Mokrushina
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  5. T. V. Bobik
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  6. T. K. Aliev
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  7. D. A. Dolgikh
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  8. M. P. Kirpichnikov
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Correspondence to D. S. Balabashin.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by A. Barkhash

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Balabashin, D.S., Kaliberda, E.N., Smirnov, I.V. et al. Development of a Serum-Free Media Based on the Optimal Combination of Recombinant Protein Additives and Hydrolysates of Non-animal Origin to Produce Immunoglobulins. Appl Biochem Microbiol 56, 595–603 (2020). https://doi.org/10.1134/S0003683820050038

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  • DOI: https://doi.org/10.1134/S0003683820050038

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