Bioprocess and Biosystems Engineering

, Volume 41, Issue 5, pp 633–640 | Cite as

Enhanced production of anti-PD1 antibody in CHO cells through transient co-transfection with anti-apoptotic genes Bcl-x L and Mcl-1

  • Xinyu Zhang
  • Lei Han
  • Huifang Zong
  • Kai Ding
  • Yuan Yuan
  • Jingyi Bai
  • Yuexian Zhou
  • Baohong Zhang
  • Jianwei Zhu
Research Paper
  • 154 Downloads

Abstract

Apoptosis has a negative impact on the cell survival state during cell cultivation. To optimize mammalian cell culture for production of biopharmaceuticals, one of the important approaches is to extend cell life through over-expression of anti-apoptotic genes. Here, we reported a cost-effective process to enhance cell survival and production of an antibody through transient co-transfection with anti-apoptotic genes Bcl-x L or Mcl-1 in Chinese hamster ovary (CHO) cells with polyethylenimine (PEI). Under the optimal conditions, it showed reduced levels of apoptosis and improved cell viability after co-transfected with Bcl-x L or Mcl-1. The overall production yield of the antibody anti-PD1 increased approximately 82% in CHO cells co-transfected with Bcl-x L , and 34% in CHO cells co-transfected with Mcl-1. This work provides an effective way to increase viability of host cells through delaying apoptosis onset, thus, raise production yield of biopharmaceuticals without the process of generating stable cell lines and subsequent screening.

Keywords

Anti-apoptosis Bcl-xL Chinese hamster ovary cell Mcl-1 Transient gene expression 

Notes

Acknowledgements

This project was supported by Natural Science Foundation of Shanghai [Grant No. 15ZR1423800].

Compliance with ethical standards

Conflict of interest

All the authors reviewed and agreed to submit this manuscript. The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

The study does not contain experiments using animals and human studies.

Supplementary material

449_2018_1898_MOESM1_ESM.tif (2.1 mb)
Supplement Fig. 1 Optimization of transfection efficiency in 3D plot showing the transfection efficiencies in CHO cells at different DNA: PEI ratios, DNA concentrations and cell concentrations. Samples were analyzed 48 h after transfection for GFP expression by flow cytometry (TIF 2139 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Xinyu Zhang
    • 1
  • Lei Han
    • 1
  • Huifang Zong
    • 1
  • Kai Ding
    • 1
  • Yuan Yuan
    • 1
  • Jingyi Bai
    • 1
  • Yuexian Zhou
    • 1
  • Baohong Zhang
    • 1
  • Jianwei Zhu
    • 1
    • 2
  1. 1.Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education; School of PharmacyShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Jecho Laboratories, Inc. 7320 Executive WayFrederickUSA

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