Bacterial Membrane Coating Potentiates Lipid Nanoparticles for mRNA Delivery.

Wang, Rui; Bao, Lin; Yu, Yiyan; Zhang, Runhe; Guo, Zhongyuan; Kubiatowicz, Luke J; Krishnan, Nishta; Noh, Ilkoo et al. · Nano Lett · 2025

basic_science · Level V

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Abstract

Bacterial outer membrane vesicles (OMVs) possess intrinsic immunostimulatory properties by carrying native antigens and pathogen-associated molecular patterns (PAMPs). Lipid nanoparticles (LNPs) have become the leading platform for messenger ribonucleic acid (mRNA) delivery, underpinning the clinical success of mRNA vaccines. Here, we developed a hybrid nanoparticle formulation, OMV-coated LNPs (OMV-LNPs), that combines the high delivery efficiency of LNPs with the immunogenicity of the OMVs to enhance gene delivery. Using <i>Escherichia coli</i>-derived OMVs and dengue virus (DENV) E80 protein as a model antigen, we generated OMV-LNPs encapsulating DENV mRNA (OMV-LNP<sub>mRNA</sub>). These nanoparticles demonstrated improved uptake by lymph-node-resident immune cells and enhanced cytosolic mRNA delivery, resulting in robust dendritic cell maturation and proinflammatory cytokine production <i>in vitro</i>. In AG129 mice, the OMV-LNP<sub>mRNA</sub> elicited significantly higher titers of DENV-neutralizing antibodies compared to conventional LNPs. Collectively, these results establish OMV-LNPs as a versatile and potent platform for effective mRNA vaccine delivery.

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