ArticleNucleic acids research2020
Systematic use of synthetic 5'-UTR RNA structures to tune protein translation improves yield and quality of complex proteins in mammalian cell factories.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- TheGenes · 2026Article
- From Structure to Function of Promoters and 5'UTRs in Maize.International journal of molecular sciences · 2026Review
- An effective method to enhance transient gene expression by transfecting high-density CHO cells.AMB Express · 2025Article
- Deciphering the determinants of recombinant protein expression across the human secretome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synthetic G-quadruplex components for predictable, precise two-level control of mammalian recombinant protein expression.Nucleic acids research · 2025Article
- From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems.International journal of molecular sciences · 2025Review
- Unraveling productivity-enhancing genes in Chinese hamster ovary cells via CRISPR activation screening using recombinase-mediated cassette exchange system.Metabolic engineering · 2025Article
- Article
- Identification of cellular signatures associated with chinese hamster ovary cell adaptation for secretion of antibodies.Computational and structural biotechnology journal · 2025Article
- Optimization of a novel expression system for recombinant protein production in CHO cells.Scientific reports · 2024Article
- The Production of Complement Inhibitor Proteins in Mammalian Cell Lines-Light at the End of the Tunnel?Biomedicines · 2024Review
- Characterization and optimization of 5´ untranslated region containing poly-adenine tracts in Kluyveromyces marxianus using machine-learning model.Microbial cell factories · 2024Article
- A Comprehensive Exploration of Bioluminescence Systems, Mechanisms, and Advanced Assays for Versatile Applications.Biochemistry research international · 2024Review
- Single-molecule imaging reveals translation-dependent destabilization of mRNAs.Molecular cell · 2023Article
- Mitochondrial dynamics and biogenesis indicators may serve as potential biomarkers for diagnosis of myasthenia gravis.Experimental and therapeutic medicine · 2022Article
- Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells.Frontiers in bioengineering and biotechnology · 2022Review
- Factors Affecting the Expression of Recombinant Protein and Improvement Strategies in Chinese Hamster Ovary Cells.Frontiers in bioengineering and biotechnology · 2022Review
- Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate.International journal of molecular sciences · 2021Review
- Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics.bioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Predictably regulating protein expression levels to improve recombinant protein production has become an important tool, but is still rarely applied to engineer mammalian cells. We therefore sought to set-up an easy-to-implement toolbox to facilitate fast and reliable regulation of protein expression in mammalian cells by introducing defined RNA hairpins, termed 'regulation elements (RgE)', in the 5'-untranslated region (UTR) to impact translation efficiency. RgEs varying in thermodynamic stability, GC-content and position were added to the 5'-UTR of a fluorescent reporter gene. Predictable translation dosage over two orders of magnitude in mammalian cell lines of hamster and human origin was confirmed by flow cytometry. Tuning heavy chain expression of an IgG with the RgEs to various levels eventually resulted in up to 3.5-fold increased titers and fewer IgG aggregates and fragments in CHO cells. Co-expression of a therapeutic Arylsulfatase-A with RgE-tuned levels of the required helper factor SUMF1 demonstrated that the maximum specific sulfatase activity was already attained at lower SUMF1 expression levels, while specific production rates steadily decreased with increasing helper expression. In summary, we show that defined 5'-UTR RNA-structures represent a valid tool to systematically tune protein expression levels in mammalian cells and eventually help to optimize recombinant protein expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.