机构:[1]Departments of Urology, Endocrinology, Orthopedic Surgery, and Gastroenterological Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China重庆医科大学附属第一医院[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA[3]Ministry of Education Key Laboratory of Diagnostic Medicine, and Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China[4]Department of Geriatrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200000, China[5]The Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing 4000430, China[6]Department of Orthopaedic Surgery, Beijing Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China[7]Department of Orthopaedic Surgery, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu 214071, China[8]Department of Orthopaedic Surgery, Benq Medical Center, The Affiliated Benq Hospital of Nanjing Medical University, Nanjing, Jiangsu 210019, China[9]Department of Orthopaedic Surgery, Yibin Second People’s Hospital, Affiliated with West China School of Medicine, Yibin, Sichuan 644000, China[10]Department of Orthopedics, Jiangxi Hospital of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China[11]Department of Oncology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261053, China[12]Stem Cell Biology and Therapy Laboratory of the Pediatric Research Institute, The National Clinical Research Center for Child Health and Disorders, and Ministry of Education Key Laboratory of Child Development and Disorders, the Children’s Hospital of Chongqing Medical University, Chongqing 400016, China[13]Division of Research and Development, Decoding Therapeutics, Inc., Mt Prospect, IL 60056, USA[14]Laboratory of Craniofacial Biology and Development, Department of Surgery Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA
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 sys<feminine ordinal indicator> 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY license (http://creativecommons.org/
基金:
Natural Science Foundation of China [82000744, 82102696]; Chongqing Bayu Young Scholar Award (China); The 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau of China) [298]; National Institutes of Health [CA226303, DE030480]; Medical Scientist Training Program of the National Institutes of Health (USA) [T32 GM007281]; University of Chicago Cancer Center Support Grant [P30CA014599]; National Center for Advancing Translational Sciences of the National Institutes of Health [2UL1TR002389-06]; Mabel Green Myers Research Endowment Fund; University of Chicago Orthopaedics Alumni Fund
第一作者机构:[1]Departments of Urology, Endocrinology, Orthopedic Surgery, and Gastroenterological Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
通讯作者:
通讯机构:[1]Departments of Urology, Endocrinology, Orthopedic Surgery, and Gastroenterological Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA[3]Ministry of Education Key Laboratory of Diagnostic Medicine, and Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China[*1]Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.[*2]Ministry of Education Key Laboratory of Diagnostic Medicine, Department of Clinical Biochemistry, School of Laboratory Medicine , Chongqing Medical University, Chongqing, 400016, China[*3]Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
推荐引用方式(GB/T 7714):
Zhao Guozhi,Zhao Piao,Wang Yonghui,et al.GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus[J].GENES & DISEASES.2024,11(6):doi:10.1016/j.gendis.2024.101344.
APA:
Zhao, Guozhi,Zhao, Piao,Wang, Yonghui,Zhang, Hui,Zhu, Yi...&Tang, Ziwei.(2024).GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus.GENES & DISEASES,11,(6)
MLA:
Zhao, Guozhi,et al."GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus".GENES & DISEASES 11..6(2024)