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作 者:Yong-Qiang Deng Na-Na Zhang Yi-Fei Zhang Xia Zhong Sue Xu Hong-Ying Qiu Tie-Cheng Wang Hui Zhao Chao Zhou Shu-Long Zu Qi Chen Tian-Shu Cao Qing Ye Hang Chi Xiang-Hui Duan Dan-Dan Lin Xiao-Jing Zhang Liang-Zhi Xie Yu-Wei Gao Bo Ying Cheng-Feng Qin
机构地区:[1]State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,AMMS,Beijing,China [2]School of Medicine,Tsinghua University,Beijing,China [3]Kunming University of Science and Technology,Kunming,Yunnan,China [4]Suzhou Abogen Biosciences Co.,Ltd,Suzhou,Jiangsu,China [5]Key laboratory of Jilin Province for Zoonosis Prevention and Control,Changchun,Jilin,China [6]Beijing Protein and Antibody R&D Engineering Center,Sinocelltech Ltd,Beijing,China.
出 处:《Cell Research》2022年第4期375-382,共8页细胞研究(英文版)
基 金:supported by the National Natural Science Foundation of China(NSFC)(82151222,82041044 and 81801583);the National Key R&D Project of China(2021YFC2302400,2020YFC0842200);C.-F.Q.was supported by the National Science Fund for Distinguished Young Scholars(81925025);the Innovative Research Group(81621005)from the NSFC;the Innovation Fund for Medical Sciences(2019-I2M-5-049)from the Chinese Academy of Medical Sciences.
摘 要:Monoclonal antibodies represent important weapons in our arsenal to against the CO VID-19 pandemic.However,this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing.Herein,we present a rapid and cost-effective lipid nanoparticle(LNP)encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies.Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27,which is currently being evaluated in clinical trials,were encapsulated into clinical grade LNP formulations(named as mRNA-HB27-LNP).I n vivo characterizatio n dem on strated that intravenous administratio n of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format.More importantly,a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1,7 and even 63 days post administration.In a close contact transmission model,prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 in fecti on betwee n hamsters in a dose-depende nt mariner.Overall,our results dem on strate a superior Ion g-term protect!on agai nst SARS-CoV-2 conferred by a single administration of this unique mRNA antibody,highlight!ng the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.
关 键 词:LIPID prevention consuming
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