2. Academic Validation
  3. Elastin-like peptides for efficient and safe delivery of mRNA

Elastin-like peptides for efficient and safe delivery of mRNA

  • J Control Release. 2025 Oct 14;388(Pt 1):114337. doi: 10.1016/j.jconrel.2025.114337.
Fei Li 1,  Quan Wang 2,  Tingting Wang 2,  Chen Xiong 2,  Ziling Chen 2,  Hanzhi Ouyang 2,  Xiaoding Lou 2,  Fan Xia 2,  Shixuan Wang 1,  Meng Wu 3,  Jun Dai 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.
  • 3 Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: mengwu@tjh.tjmu.edu.cn.
  • 4 Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: jundai@tjh.tjmu.edu.cn.
PMID: 41101699 DOI: 10.1016/j.jconrel.2025.114337
Abstract

mRNA vaccines represent a significant advancement in the field of Cancer treatment and prevention. Nevertheless, challenges persist in optimizing mRNA transfection efficiency and mitigating associated side effects. In this study, we have developed a genetically engineered modular elastin-like peptide (ELP), designated V20K40L. The V20 module is hydrophobic, while K40 is hydrophilic and highly positively charged. These modules self-assemble with Melan-A mRNA (M) and CpG (C) to form nanocomposites (MC@V20K40L). Due to the inverse transition cycling effect, MC@V20K40L transitions from a loose to a tight conformation in response to physiological temperature (37 °C), enhancing its stability. The nanocomposites exhibit multiple cellular entry pathways, including endocytosis and macropinocytosis, thereby improving cellular uptake efficiency. Moreover, under the synergistic effect of the KALA peptide (L) and K40, MC@V20K40L efficiently escapes lysosomes and translates more antigens, thereby boosting antigen delivery and immune memory. Compared to DOTAP/mRNA lipoplexes (MC@DOTAP), MC@V20K40L demonstrates a 400 % increase in mRNA transfection efficiency, with a concomitant reduction in inflammatory responses. These genetically engineered ELPs promote efficient delivery of mRNA, increase transfection efficiency, and also mitigate side effects, offering great translational potential for mRNA vaccines.

Keywords

Elastin-like polypeptide; Genetic engineering; Lipid nanoparticle; mRNA delivery; mRNA vaccine.

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