ACS nanoJan 19, 2026

A virus-like carrier that fuses twice to deliver mRNA vaccines directly into immune cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

A dual-fusogenic virus-like particle may improve mRNA vaccine delivery by targeting dendritic cells and boosting antigen-specific immune responses in preclinical models.

Evidence

This preclinical platform study tested DC/E-FVLPs in cell and mouse experiments, reporting 28.2% cytosolic mRNA delivery and immune responses at 50 ng mRNA per mouse.

Caveat

The evidence is limited to preclinical delivery and immune-response endpoints, without human safety or disease-protection outcomes.

Simplified

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-FVLPselectively 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-FVLPmarkedly 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-FVLPefficiently induces both cellular and humoral immune responses against SARS-CoV-2 antigens and solid tumors. Thus, DC/E-FVLPholds promise as a potent mRNA vaccine delivery vehicle. mRNA mRNA mRNA mRNA