信使核糖核酸
刺
癌症免疫疗法
免疫
免疫疗法
干扰素基因刺激剂
RNA干扰
生物
癌症研究
抗原
药理学
免疫学
免疫系统
细胞生物学
核糖核酸
先天免疫系统
基因
生物化学
工程类
航空航天工程
作者
Lihua Zhou,Wenzhe Yi,Zehong Zhang,Xiaoting Shan,Zitong Zhao,Xiangshi Sun,Jue Wang,Hao Wang,Hualiang Jiang,Mingyue Zheng,Dangge Wang,Yaping Li
摘要
Messenger RNA (mRNA) vaccine is revolutionizing the methodology of immunization in cancer. However, mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport, rapid clearance, catalytic hydrolysis, insufficient cellular entry and endosome entrapment. Herein, we design a mRNA nanovaccine based on intelligent design to overcome these obstacles. Highly efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers, ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) to targets. It activates stimulator of interferon genes (STING), promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo, thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing mice. This work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization, with great translational potential for enhancing cancer immunotherapy.
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