دورية أكاديمية
Developing microRNAs as engineering tools to modulate monoclonal antibody galactosylation.
| العنوان: | Developing microRNAs as engineering tools to modulate monoclonal antibody galactosylation. |
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| المؤلفون: | Klingler, Florian, Schlossbauer, Patrick, Naumann, Lukas, Handrick, René, Hesse, Friedemann, Neusüß, Christian, Otte, Kerstin |
| المصدر: | Biotechnology & Bioengineering; Apr2024, Vol. 121 Issue 4, p1355-1365, 11p |
| مستخلص: | N‐linked glycosylation is one of the most important post‐translational modifications of monoclonal antibodies (mAbs) and is considered to be a critical quality attribute (CQA), as the glycan composition often has immunomodulatory effects. Since terminal galactose residues of mAbs can affect antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytolysis (CDC) activation, serum half‐life, and antiviral activity it has to be monitored, controlled and modulated to ensure therapeutic effects. The ability of small noncoding microRNAs (miRNAs) to modulate glycosylation in Chinese hamster ovary (CHO) production cells was recently reported establishing miRNAs as engineering tools for modulation of protein glycosylation. In this study, we report the characterization and validation of miRNAs as engineering tools for increased (mmu‐miR‐452‐5p, mmu‐miR‐193b‐3p) or decreased (mmu‐miR‐7646‐5p, mmu‐miR‐7243‐3p, mmu‐miR‐1668, mmu‐let‐7c‐1‐3p, mmu‐miR‐7665‐3p, mmu‐miR‐6403) degree of galactosylation. Furthermore, the biological mode of action regulating gene expression of the galactosylation pathway was characterized as well as their influence on bioprocess‐related parameters. Most important, stable plasmid‐based overexpression of these miRNAs represents a versatile tool for engineering N‐linked galactosylation to achieve favorable phenotypes in cell lines for biopharmaceutical production. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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