| Autor: |
Guozhi Zhao, Piao Zhao, Yonghui Wang, Hui Zhang, Yi Zhu, Jiamin Zhong, Wulin You, Guowei Shen, Changqi Luo, Ou Mei, Xingye Wu, Jingjing Li, Yi Shu, Hongwei Wang, William Wagstaff, Hue H. Luu, Yang Bi, Lewis L. Shi, Russell R. Reid, Tong-Chuan He, Li Jiang, Wei Tang, Jiaming Fan, Ziwei Tang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Genes and Diseases, Vol 11, Iss 6, Pp 101344- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3042 |
| DOI: |
10.1016/j.gendis.2024.101344 |
| Popis: |
Recombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production. By stably overexpressing GAPDH in HEK293 (293G) and 293pTP (293GP) cells, respectively, we demonstrated that rAdV-induced ROS production and cell apoptosis were significantly suppressed in 293G and 293GP cells. Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells. Similarly, Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells. We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells. 293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells, indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production. These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production. Therefore, the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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