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The effect of Ccnb1ip1 insulator on monoclonal antibody expression in Chinese hamster ovary cells

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Abstract

Background

The increasing need for therapeutic monoclonal antibodies (mAbs) entails the development of innovative and improved expression strategies. Chromatin insulators have been utilized for the enhancement of the heterologous proteins in mammalian cells.

Methods and results

In the current study the Ccnb1ip1 gene insulator element was utilized to construct a novel vector system for the expression of an anti-CD52 mAb in Chinese hamster ovary (CHO) cells. The insulator containing (pIns-mAb) and control (pmAb) vectors were generated and stable cell pools were established using these constructs. The expression level in the cells created with pIns-mAb vector was calculated to be 233 ng/mL, and the expression rate in the control vector was 210 ng/mL, which indicated a 10.9% increase in mAb expression in pIns-mAb pool. In addition, analysis of mAb expression in clonal cells established from each pool showed a 10% increase in antibody productivity in the highest mAb producing clone derived from the pIns-mAb pool compared to the clone isolated from pmAb pool.

Conclusions

More studies are needed to fully elucidate the effects of Ccnb1ip1 gene insulator on recombinant therapeutic protein expression in mammalian cells. The combination of this element with other chromatin-modifying elements might improve its augmentation effect which could pave the way for efficient and cost-effective production of therapeutic drugs.

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Acknowledgements

The authors wish to thank Medical Nano-Technology & Tissue Engineering Research Center and School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Funding

This study was funded by the “the Arak University of Medical Sciences” (Grant Number: 3150).

Author information

Authors and Affiliations

  1. Medical Nano-Technology & Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azam Rahimpour & Es’hagh Pourmaleki

  2. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azam Rahimpour & Es’hagh Pourmaleki

  3. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Forough Shams

  4. Immunology Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Zahra Payandeh

  5. Biochemistry Department, Guilan University of Medical Sciences, Rasht, Iran

    Navid Pourzardosht

  6. Department of Medical Parasitology and Mycology, School of Medicine, Arak University of Medical Sciences, Arāk, Iran

    Mojtaba Didehdar

  7. Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arāk, Iran

    Milad Gholami

Authors
  1. Azam Rahimpour
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  2. Es’hagh Pourmaleki
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  3. Forough Shams
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  4. Zahra Payandeh
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  5. Navid Pourzardosht
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  6. Mojtaba Didehdar
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  7. Milad Gholami
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Contributions

Authors participated in conception and design (AR, MG, EP and MD), data collection and statistical analysis (AR, MG, FS, ZP and NP), performing experiments (AR, EP, FS, ZP, NP, MD and MG), and drafting the article or revising critically for important intellectual content (AR, EP, FS, ZP, NP, MD and MG).

Corresponding author

Correspondence to Milad Gholami.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethics committee at Arak University of Medical Sciences (IR.ARAKMU.REC.1397.128).

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Rahimpour, A., Pourmaleki, E., Shams, F. et al. The effect of Ccnb1ip1 insulator on monoclonal antibody expression in Chinese hamster ovary cells. Mol Biol Rep 49, 3461–3468 (2022). https://doi.org/10.1007/s11033-022-07182-x

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  • DOI: https://doi.org/10.1007/s11033-022-07182-x

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