Stable overexpression of native and artificial miRNAs for the production of differentially fucosylated antibodies in CHO cells.

Autor: Schlossbauer P; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany., Naumann L; Department of Chemistry Aalen University Aalen Germany., Klingler F; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany., Burkhart M; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany., Handrick R; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany., Korff K; Department of Chemistry Aalen University Aalen Germany., Neusüß C; Department of Chemistry Aalen University Aalen Germany., Otte K; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany., Hesse F; Institute for Applied Biotechnology University of Applied Sciences Biberach Biberach Germany.
Jazyk: angličtina
Zdroj: Engineering in life sciences [Eng Life Sci] 2024 Apr 01; Vol. 24 (6), pp. 2300234. Date of Electronic Publication: 2024 Apr 01 (Print Publication: 2024).
DOI: 10.1002/elsc.202300234
Abstrakt: Cell engineering strategies typically rely on energy-consuming overexpression of genes or radical gene-knock out. Both strategies are not particularly convenient for the generation of slightly modulated phenotypes, as needed in biosimilar development of for example differentially fucosylated monoclonal antibodies (mAbs). Recently, transiently transfected small noncoding microRNAs (miRNAs), known to be regulators of entire gene networks, have emerged as potent fucosylation modulators in Chinese hamster ovary (CHO) production cells. Here, we demonstrate the applicability of stable miRNA overexpression in CHO production cells to adjust the fucosylation pattern of mAbs as a model phenotype. For this purpose, we applied a miRNA chaining strategy to achieve adjustability of fucosylation in stable cell pools. In addition, we were able to implement recently developed artificial miRNAs (amiRNAs) based on native miRNA sequences into a stable CHO expression system to even further fine-tune fucosylation regulation. Our results demonstrate the potential of miRNAs as a versatile tool to control mAb fucosylation in CHO production cells without adverse side effects on important process parameters.
Competing Interests: The authors declare no conflicts of interest.
(© 2024 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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