Language

English

Publication Date

1-13-2025

Journal

Molecular Cancer

DOI

10.1186/s12943-024-02211-8

PMID

39806486

PMCID

PMC11727718

PubMedCentral® Posted Date

1-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity. Notably, a DNA vaccine encoding the spike protein, delivered via LNP-M, induced stronger antigen-specific antibody and T cell immune responses compared to electroporation. Single-cell RNA sequencing (scRNA-seq) analysis revealed that the LNP-M/pSpike vaccine enhanced CD80 activation signaling in CD8

Keywords

Animals, Mice, Nanoparticles, Vaccines, DNA, Humans, Lipids, DNA, Female, CD8-Positive T-Lymphocytes, Biological Products, Liposomes, Lipid nanoparticles, DNA-encoded biologics, Vaccines, Monoclonal antibodies, Cancer immunotherapy

Published Open-Access

yes

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