Tumorigenicity decrease in Bcl-xL deficient MDCK cells ensuring the safety for influenza vaccine production.

Autor: Zheng J; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Li B; Medical Products Administration of Hubei Province, Wuhan, China., Jia L; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Zhang J; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Gong Z; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Le Y; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Nian X; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Li X; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Liu B; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Yu D; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Zhang Z; National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.; Wuhan Institute of Biological Products Co.Ltd., Wuhan, China., Li C; National Institute for Food and Drug Control, Beijing, China.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Dec 16; Vol. 19 (12), pp. e0311069. Date of Electronic Publication: 2024 Dec 16 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0311069
Abstrakt: Madin-Darby canine kidney (MDCK) cells are the recognized cell strain for influenza vaccine production. However, the tumorigenic potential of MDCK cells raises concerns about their use in biological product manufacturing. To reduce MDCK cells' tumorigenicity and ensure the safety of influenza vaccine production, a B-cell lymphoma extra-large (Bcl-xL) gene, which plays a pivotal role in apoptosis regulation, was knocked-out in original MDCK cells by CRISPR-Cas9 gene editing technology, so that a homozygous MDCK-Bcl-xL-/- cell strain was acquired and named as BY-02. Compared with original MDCK cells, the proliferation and migration ability of BY-02 were significantly reduced, while apoptosis level was significantly increased, the endogenous mitochondrial apoptotic pathway were also modulated after Bcl-xL knock-out in MDCK cells. For tumor formation assays in nude mouse tests, all ten mice injected with original MDCK cells presented tumors growth in the injection site, in contrast to only one mouse injected with BY-02 cells presented tumors growth. These findings suggest that Bcl-xL knock-down is an effective strategy to inhibit tumor formation in MDCK cells, making BY-02 a promising genetically engineered cell strain for influenza vaccine production.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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