STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy

• Published in: National science review 2023-10, Vol.10 (10), p.nwad214-nwad214
• Main Authors: Zhou, Lei, Yi, Wenzhe, Zhang, Zehong, Shan, Xiaoting, Zhao, Zitong, Sun, Xiangshi, Wang, Jue, Wang, Hao, Jiang, Hualiang, Zheng, Mingyue, Wang, Dangge, Li, Yaping
• Format: Article
• Language: English
• ISSN: 2095-5138; 2053-714X
• DOI: 10.1093/nsr/nwad214

ABSTRACT 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. This paper provides a rational design option to develop mRNA nanovaccine with machine learning techniques, leading to effective stimulator of interferon genes (STING) agonist-synergized mRNA immunization.