Citation: Shengbin Liu, Haixing Shi, Danni Dai, Tingchen Tian, Xing Duan, Ju Sun, Weitong Xu, Xiaoling Yin, Yongmei Xie, Xiangrong Song. mRNA-based vaccines: Rational antigen design, delivery optimization, and immune modulation[J]. Chinese Chemical Letters, ;2026, 37(12): 112312. doi: 10.1016/j.cclet.2025.112312 shu

mRNA-based vaccines: Rational antigen design, delivery optimization, and immune modulation

Shengbin Liu ^{a, 1} ,
Haixing Shi ^{a, 1} ,
Danni Dai ^{b, 1} ,
Tingchen Tian ^c ,
Xing Duan ^a ,
Ju Sun ^a ,
Weitong Xu ^a ,
Xiaoling Yin ^a ,
Yongmei Xie ^{a, *,} ,
Xiangrong Song ^{a, *,}

a.
Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
b.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
c.
West China School of Pharmacy, Sichuan University, Chengdu 610041, China

xieym@scu.edu.cn

songxr@scu.edu.cn

Received Date: 27 August 2025
Revised Date: 20 December 2025
Accepted Date: 22 December 2025
Available Online: 23 December 2025

Figures(7)

The proven clinical efficacy of messenger RNA (mRNA) vaccines against corona virus disease 2019 (COVID-19) has accelerated the development of mRNA nanomedicines for diverse therapeutic applications. Nevertheless, knowledge gaps persist, constraining the development of next-generation mRNA therapeutics with enhanced potency and safety. Deeper insights into the mechanisms of mRNA vaccine effects, coupled with rational antigen design, innovative delivery strategies, and optimized vaccination regimens, are essential for producing highly effective therapies against a broad spectrum of diseases. This review commences by outlining current advances in mRNA modification, synthesis, novel lipids design, and alternative nanoparticles development for mRNA-based vaccines. Subsequently, it covers targeted delivery systems, emphasizing endosomal escape and cell- or organ-specific targeting. Additionally, we deliberate on the potential challenges mRNA drugs face in disease treatment, current improvement endeavors, and future application prospects. Furthermore, we highlight emerging systems immunology approaches that integrate multi-omic and computational analyses to elucidate human immune responses to vaccination and enhance predictive modeling. Finally, we summarize key points pertaining to the preclinical and clinical development of mRNA therapeutics. Overall, this review strives to provide a comprehensive understanding of mRNA-based therapies while illuminating prospective development and clinical applications.
- mRNA,
- Delivery system,
- Targeted therapy,
- Cancer and infectious diseases,
- Precision medicine
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