ArticleScientific reports2019
A human expression system based on HEK293 for the stable production of recombinant erythropoietin.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies.American journal of human genetics · 2022Pooled it
- Streamlined rAAV HeLaS3 producer cell line generation via GS selection.Scientific reports · 2026Article
- Structural Analysis of Membrane Proteins in Cell-Derived Microvesicles.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Cell Engineering for Increasing Production of Recombinant Proteins in Mammalian Cells.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Screening and characterization of monoclonal antibodies with neutralizing activity against porcine transmissible gastroenteritis virus.BMC veterinary research · 2025Article
- Advances in Serum-Free Suspension Culture Technology for Animal Cells and Their Applications.Vaccines · 2025Review
- Production of Clinical-Grade SARS-CoV-2 Spike Ferritin Nanoparticle Protein Immunogen by Transient Transfection.Vaccines · 2025Article
- Unveiling the Accurate Site-SpecificAnalytical chemistry · 2025Article
- Genomic landscape of breast cancer in elderly patients.NPJ breast cancer · 2025Article
- Development of Recombinant Antibodies and Its Application in Immunomagnetic Separation-Based Rapid Detection ofJournal of microbiology and biotechnology · 2024Article
- Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.American journal of human genetics · 2024Article
- Transient Expression in HEK-293 Cells in Suspension Culture as a Rapid and Powerful Tool: SARS-CoV-2 N and Chimeric SARS-CoV-2N-CD154 Proteins as a Case Study.Biomedicines · 2023Article
- Improvement of HEK293 Cell Growth by Adapting Hydrodynamic Stress and Predicting Cell Aggregate Size Distribution.Bioengineering (Basel, Switzerland) · 2023Article
- Comparison of vector elements and process conditions in transient and stable suspension HEK293 platforms using SARS-CoV-2 receptor binding domain as a model protein.BMC biotechnology · 2023Article
- - Invited Review - Gene-editing techniques and their applications in livestock and beyond.Animal bioscience · 2023Article
- Slight Variations in the Sequence Downstream of the Polyadenylation Signal Significantly Increase Transgene Expression in HEK293T and CHO Cells.International journal of molecular sciences · 2022Article
- Designing and characterization of a SARS-CoV-2 immunogen with receptor binding motif grafted on a protein scaffold: An epitope-focused vaccine approach.International journal of biological macromolecules · 2022Article
- Engineering and validation of a dual luciferase reporter system for quantitative and systematic assessment of regulatory sequences in Chinese hamster ovary cells.Scientific reports · 2022Article
- Discovery and validation of human genomic safe harbor sites for gene and cell therapies.Cell reports methods · 2022Article
- New Opportunities in Glycan Engineering for Therapeutic Proteins.Antibodies (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian host cell lines are the preferred expression systems for the manufacture of complex therapeutics and recombinant proteins. However, the most utilized mammalian host systems, namely Chinese hamster ovary (CHO), Sp2/0 and NS0 mouse myeloma cells, can produce glycoproteins with non-human glycans that may potentially illicit immunogenic responses. Hence, we developed a fully human expression system based on HEK293 cells for the stable and high titer production of recombinant proteins by first knocking out GLUL (encoding glutamine synthetase) using CRISPR-Cas9 system. Expression vectors using human GLUL as selection marker were then generated, with recombinant human erythropoietin (EPO) as our model protein. Selection was performed using methionine sulfoximine (MSX) to select for high EPO expression cells. EPO production of up to 92700 U/mL of EPO as analyzed by ELISA or 696 mg/L by densitometry was demonstrated in a 2 L stirred-tank fed batch bioreactor. Mass spectrometry analysis revealed that N-glycosylation of the produced EPO was similar to endogenous human proteins and non-human glycan epitopes were not detected. Collectively, our results highlight the use of a human cellular expression system for the high titer and xenogeneic-free production of EPO and possibly other complex recombinant proteins.
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