DNA tetrahedron nanoparticles service as a help carrier and adjvant of mRNA vaccine.

Abstract

Aim of the study: To investigate the potential of DNA nanoparticles (DNPs) as carriers and adjuvants for mRNA vaccines.

Materials and methods: Customized oligonucleotides were assembled into DNA tetrahedra (DNA-TH), which were subsequently complexed with streptavidin and mRNA encoding green fluorescent protein (GFP). Various assays were conducted to evaluat the stability of the DNPs, their cellular uptake, immune activation potential, and GFP mRNA transcription efficiency. P53-mutant HSC-3 cells were used to establish a subcutaneous xenograft tumor model to explore the effects of DNPs as carriers and adjuvants in a disease model.

Results: The DNPs were remained stable extracellularly and rapidly taken up by antigen-presenting cells. Compared to naked GFP mRNA, DNPs statistically significantly activated immune responses and facilitated GFP mRNA transcription and protein expression both in vitro and in vivo. Immunization with DNP-GFP mRNA complexes induced higher antibody titers compared to naked mRNA. The DNPs demonstrated good biocompatibility. DNP-p53 inhibited the growth of subcutaneous xenograft tumors in mice with p53-mutant HSC-3 cells, outperforming both the naked p53 mRNA and blank control groups, with a statistically significant difference (P < 0.05).

Conclusion: DNA nanoparticles show promise for improving mRNA vaccine delivery and efficacy. Further optimization of these nanoparticles could lead to highly effective mRNA vaccine carriers with broad applications.