Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
J Transl Med. 2024 Nov 14;22(1):1024. doi: 10.1186/s12967-024-05837-w.
To investigate the potential of DNA nanoparticles (DNPs) as carriers and adjuvants for mRNA vaccines.
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.
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).
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.
研究 DNA 纳米颗粒（DNPs）作为 mRNA 疫苗载体和佐剂的潜力。
定制的寡核苷酸被组装成 DNA 四面体（DNA-TH），随后与链霉亲和素和编码绿色荧光蛋白（GFP）的 mRNA 复合。进行了各种实验来评估 DNPs 的稳定性、细胞摄取能力、免疫激活潜力和 GFP mRNA 转录效率。使用 p53 突变 HSC-3 细胞建立皮下异种移植肿瘤模型，以探讨 DNPs 作为载体和佐剂在疾病模型中的作用。
DNPs 在细胞外保持稳定，并被抗原呈递细胞迅速摄取。与裸露的 GFP mRNA 相比，DNPs 在体外和体内均能显著激活免疫反应，并促进 GFP mRNA 转录和蛋白表达。与裸露 mRNA 相比，DNP-GFP mRNA 复合物的免疫接种诱导了更高的抗体滴度。DNPs 表现出良好的生物相容性。DNP-p53 抑制了携带 p53 突变的 HSC-3 细胞的皮下异种移植肿瘤的生长，优于裸露的 p53 mRNA 和空白对照组，差异具有统计学意义（P<0.05）。
DNA 纳米颗粒显示出改善 mRNA 疫苗传递和疗效的潜力。进一步优化这些纳米颗粒可能会导致具有广泛应用前景的高效 mRNA 疫苗载体。
