2. Academic Validation
  3. A Polymeric mRNA Vaccine Featuring Enhanced Site-Specific mRNA Delivery and Inherent STING-Stimulating Performance for Tumor Immunotherapy

A Polymeric mRNA Vaccine Featuring Enhanced Site-Specific mRNA Delivery and Inherent STING-Stimulating Performance for Tumor Immunotherapy

  • Adv Mater. 2025 Mar 17:e2410998. doi: 10.1002/adma.202410998.
Xiaoya Guo 1 2,  Zhiyu Yang 1 2,  Zhaopei Guo 1,  Huiyan Lai 3,  Hanyu Meng 3,  Meng Meng 1 2,  Tong Li 1 2,  Zhen Li 3,  Jie Chen 1,  Yuanji Feng 3,  Xuan Pang 1 2,  Huayu Tian 1 2 3,  Xuesi Chen 1 2
Affiliations

Affiliations

  • 1 Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
  • 2 School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.
  • 3 State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen, 361005, China.
PMID: 40095378 DOI: 10.1002/adma.202410998
Abstract

The development of mRNA delivery carriers with innate immune stimulation functions has emerged as a focal point in the field of mRNA vaccines. Nonetheless, the expression of mRNA in specific sites and innate immune stimulation at specific sites are prerequisites for ensuring the safety of mRNA vaccines. Based on the synthetic PEIRs carriers library, this study identifies an innovative mRNA delivery carrier named POctS with the following characteristics: 1) simultaneously possessing high mRNA delivery efficiency and stimulator of interferon genes (STING) stimulation function. 2) Leveraging the distinctive site-specific delivery capabilities of POctS, the expression of mRNA at specific sites and the activation of innate immune responses at designated sites are achieved, minimizing formulation toxicity and maximizing the vaccine performance. 3) Tailoring two types of mRNA vaccines based on POctS according to the immune infiltration status of different types of tumors. Briefly, POctS-loading ovalbumin (OVA) mRNA as a tumor antigen vaccine achieves the prevention and treatment of melanoma in mice. Further, POctS-loading Mixed Lineage Kinase domain-like protein (MLKL) mRNA as an in situ tumor vaccine effectively treats orthotopic pancreatic Cancer in mice. This delivery carrier offers a feasible mRNA vaccine-based immunotherapy strategy for various types of tumors.

Keywords

STING‐stimulating; cancer immunotherapy; mRNA vaccines; site‐specific delivery.

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