2. Academic Validation
  3. A Dual-Fusogenic Virus-like Vector Enables Direct Cytosolic Delivery of mRNA Vaccines to Dendritic Cells

A Dual-Fusogenic Virus-like Vector Enables Direct Cytosolic Delivery of mRNA Vaccines to Dendritic Cells

  • ACS Nano. 2026 Feb 3;20(4):3551-3564. doi: 10.1021/acsnano.5c16068.
Yi-Fang Chen 1 2,  Shi-Kun Zhou 1,  Qiu-Hong Jian 1,  Min Yang 1,  Li Li Chen 1,  Shui-Qing Jiang 1,  Cong-Fei Xu 1 3,  Jun Wang 1 3
Affiliations

Affiliations

  • 1 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, P. R. China.
  • 2 Department of Pharmacy and Pharmaceutic Sciences, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117559, Singapore.
  • 3 National Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, P. R. China.
PMID: 41549530 DOI: 10.1021/acsnano.5c16068
Abstract

Messenger RNA (mRNA) vaccines hold significant potential for disease prevention and treatment; however, their effectiveness is limited by the inefficiency of current carriers in targeting dendritic cells (DCs) and facilitating endosomal escape to deliver mRNA into the cytosol. In this study, we develop a dual-fusogenic virus-like particle (VLP) cofunctionalized with a DC-targeting fusogen (DC-F) and an endosomal fusogen (E-F), termed DC/E-FVLP. We show that mRNA-loaded DC/E-FVLPmRNA selectively targets DCs and promotes fusion with both the plasma and endosomal membranes, achieving a 28.2% mRNA cytosolic delivery efficiency, which is approximately 60 times greater than that of lipid nanoparticles (LNP). Subcutaneous injection of DC/E-FVLPmRNA markedly enhances mRNA delivery to DCs in lymph nodes, resulting in improved antigen expression and presentation. At a dose of 50 ng mRNA per mouse, DC/E-FVLPmRNA efficiently induces both cellular and humoral immune responses against SARS-CoV-2 antigens and solid tumors. Thus, DC/E-FVLPmRNA holds promise as a potent mRNA vaccine delivery vehicle.

Keywords

cancer vaccine; endosome escape; mRNA vaccine; membrane fusion; virus-like particle.

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