Gonzalez-Rivera JC, Galvan A, Ryder T, Milman M, Agarwal K, Kandari L, et al. A high-titer scalable Chinese hamster ovary transient expression platform for production of biotherapeutics. Biotechnol Bioeng. 2024;121(11):3454–70. https://doi.org/10.1002/bit.28817.
Article CAS PubMed Google Scholar
Beygmoradi A, Homaei A, Hemmati R, Fernandes P. Recombinant protein expression: challenges in production and folding related matters. Int J Biol Macromol. 2023;233:123407. https://doi.org/10.1016/j.ijbiomac.2023.123407.
Article CAS PubMed Google Scholar
Mordor Intelligence. Biopharmaceutical industry size & share analysis—growth trends & forecasts (2025–2030). https://www.mordorintelligence.com/industry-reports/global-biopharmaceuticals-market-industry. Accessed 7 Nov 2025.
O’Flaherty R, Bergin A, Flampouri E, Mota LM, Obaidi I, Quigley A, et al. Mammalian cell culture for production of recombinant proteins: a review of the critical steps in their biomanufacturing. Biotechnol Adv. 2020;43:107552. https://doi.org/10.1016/j.biotechadv.2020.107552.
Article CAS PubMed Google Scholar
Guo X, Wang C, Wang TY. Chromatin-modifying elements for recombinant protein production in mammalian cell systems. Crit Rev Biotechnol. 2020;40(7):1035–43. https://doi.org/10.1080/07388551.2020.1805401.
Article CAS PubMed Google Scholar
Wang TY, Guo X. Expression vector cassette engineering for recombinant therapeutic production in mammalian cell systems. Appl Microbiol Biotechnol. 2020;104(13):5673–88. https://doi.org/10.1007/s00253-020-10640-w.
Article CAS PubMed Google Scholar
Grand View Research. Monoclonal Antibodies Market (2023–2030). https://www.grandviewresearch.com/industry-analysis/monoclonal-antibodies-market. Accessed 7 Nov 2025.
Lalonde ME, Durocher Y. Therapeutic glycoprotein production in mammalian cells. J Biotechnol. 2017;251:128–40. https://doi.org/10.1016/j.jbiotec.2017.04.028.
Article CAS PubMed Google Scholar
Malm M, Kuo CC, Barzadd MM, Mebrahtu A, Wistbacka N, Razavi R, et al. Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins. Metab Eng. 2022;72:171–87. https://doi.org/10.1016/j.ymben.2022.03.009.
Article CAS PubMed PubMed Central Google Scholar
Cao XX, Yuan JJ, Bai ZY, Zhang M, Yun YF, Wang XY, et al. Effect of CHO cell line constructed with CMAH gene-directed integration on the recombinant protein expression. Int J Biol Macromol. 2025;292:139274. https://doi.org/10.1016/j.ijbiomac.2024.139274.
Article CAS PubMed Google Scholar
Zeh N, Schmidt M, Schulz P, Fischer S. The new frontier in CHO cell line development: from random to targeted transgene integration technologies. Biotechnol Adv. 2024;75:108402. https://doi.org/10.1016/j.biotechadv.2024.108402.
Article CAS PubMed Google Scholar
Eisenhut P, Marx N, Borsi G, Papež M, Ruggeri C, Baumann M, et al. Manipulating gene expression levels in mammalian cell factories: an outline of synthetic molecular toolboxes to achieve multiplexed control. New Biotechnol. 2024;79:1–19. https://doi.org/10.1016/j.nbt.2023.11.003.
Liu HN, Dong WH, Lin Y, Zhang ZH, Wang TY. The effect of microRNA on the production of recombinant protein in CHO cells and its mechanism. Front Bioeng Biotechnol. 2022;10:832065. https://doi.org/10.3389/fbioe.2022.832065.
Article PubMed PubMed Central Google Scholar
Pulix M, Lukashchuk V, Smith DC, Dickson AJ. Molecular characterization of HEK293 cells as emerging versatile cell factories. Curr Opin Biotechnol. 2021;71:18–24. https://doi.org/10.1016/j.copbio.2021.05.001.
Article CAS PubMed Google Scholar
Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–4. https://doi.org/10.1038/nature09807.
Article CAS PubMed PubMed Central Google Scholar
Xu N, Ma C, Ou J, Sun WW, Zhou L, Hu H, et al. Comparative proteomic analysis of three Chinese hamster ovary (CHO) host cells. Biochem Eng J. 2017;124:122–9. https://doi.org/10.1016/j.bej.2017.05.007.
Article CAS PubMed PubMed Central Google Scholar
Tan E, Chin CSH, Lim ZFS, Ng SK. HEK293 cell line as a platform to produce recombinant proteins and viral vectors. Front Bioeng Biotechnol. 2021;9:796991. https://doi.org/10.3389/fbioe.2021.796991.
Article PubMed PubMed Central Google Scholar
Zhou J, Yan GG, Cluckey D, Meade C, Ruth M, Sorm R, et al. Exploring parametric and mechanistic differences between Expi293FTM and ExpiCHO-STM cells for transient antibody production optimization. Antibodies. 2023;12(3):53. https://doi.org/10.3390/antib12030053.
Article CAS PubMed PubMed Central Google Scholar
Zhao Y, Li H, Fan Z, Wang T. Effect of host cell protein on Chinese hamster ovary recombinant protein production and its removal strategies: a mini review. Curr Pharm Biotechnol. 2024;25(6):665–75. https://doi.org/10.2174/1389201024666230818112633.
Article CAS PubMed Google Scholar
Yang YX, Li Q, Li WD, Wang TY, Feng HG. Factors and mechanisms affecting the secretion of recombinant protein in CHO cells. Curr Pharm Biotechnol. 2023;24(3):391–400. https://doi.org/10.2174/1389201023666220603121316.
Article CAS PubMed Google Scholar
Bachhav B, de Rossi J, Llanos CD, Segatori L. Cell factory engineering: challenges and opportunities for synthetic biology applications. Biotechnol Bioeng. 2023;120(9):2441–59. https://doi.org/10.1002/bit.28365.
Article CAS PubMed PubMed Central Google Scholar
Fischer S, Handrick R, Otte K. The art of CHO cell engineering: a comprehensive retrospect and future perspectives. Biotechnol Adv. 2015;33(8):1878–96. https://doi.org/10.1016/j.biotechadv.2015.10.015.
Article CAS PubMed Google Scholar
Donaldson JS, Dale MP, Rosser SJ. Decoupling growth and protein production in CHO cells: a targeted approach. Front Bioeng Biotechnol. 2021;9:658325. https://doi.org/10.3389/fbioe.2021.658325.
Article PubMed PubMed Central Google Scholar
Backliwal G, Hildinger M, Chenuet S, Wulhfard S, De Jesus M, Wurm FM. Rational vector design and multi-pathway modulation of HEK 293E cells yield recombinant antibody titers exceeding 1 g/l by transient transfection under serum-free conditions. Nucleic Acids Res. 2008;36(15):e96. https://doi.org/10.1093/nar/gkn423.
Article CAS PubMed PubMed Central Google Scholar
Werner NS, Weber W, Fussenegger M, Geisse S. A gas-inducible expression system in HEK.EBNA cells applied to controlled proliferation studies by expression of p27(Kip1). Biotechnol Bioeng. 2007;96(6):1155–66. https://doi.org/10.1002/bit.21235.
Article CAS PubMed Google Scholar
Jaluria P, Betenbaugh M, Konstantopoulos K, Shiloach J. Enhancement of cell proliferation in various mammalian cell lines by gene insertion of a cyclin-dependent kinase homolog. BMC Biotechnol. 2007;7:71. https://doi.org/10.1186/1472-6750-7-71.
Article CAS PubMed PubMed Central Google Scholar
Latorre Y, Torres M, Vergara M, Berrios J, Sampayo MM, Gödecke N, et al. Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production. Sci Rep. 2023;13(1):1482. https://doi.org/10.1038/s41598-023-28622-z.
Article CAS PubMed PubMed Central Google Scholar
Roobol A, Roobol J, Smith ME, Carden MJ, Hershey JWB, Willis AE, et al. Engineered transient and stable overexpression of translation factors eIF3i and eIF3c in CHOK1 and HEK293 cells gives enhanced cell growth associated with increased c-Myc expression and increased recombinant protein synthesis. Metab Eng. 2020;59:98–105. https://doi.org/10.1016/j.ymben.2020.02.001.
Comments (0)