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针对SARS-CoV-2的循环RNA脂质纳米粒子疫苗

Kelsey L Swingle¹, Alex G Hamilton¹, Xuexiang Han¹

¹Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.

Proceedings of the National Academy of Sciences of the United States of America

|September 15, 2025

概括

通过脂质纳米颗粒 (LNP) 输送的循环RNA (circRNA) 疫苗与信使RNA (mRNA) 疫苗相比,显示出增强的稳定性和免疫性. 这种优化的circRNA LNP平台为传染病疫苗接种提供了一个有希望的新方法.

科学领域:

生物技术是生物技术.
疫苗学疫苗学疫苗学
免疫学免疫学免疫学

背景情况:

使者RNA (mRNA) 疫苗广泛用于SARS-CoV-2,但循环RNA (circRNA) 提供了潜在的优势,如增加稳定性和降低免疫性.
对于circRNA的细胞内传递技术仍然不发达,这阻碍了其疫苗应用.

研究的目的:

开发一个优化的脂质纳米粒子 (LNP) 平台,用于有效的蛋白质编码circRNA的细胞内传递.
在临床前模型中评估针对SARS-CoV-2的基于circRNA的疫苗的疗效.

主要方法:

使用实验设计 (DoE) 方法来优化circRNA LNP配方参数.
评估了circRNA LNP传递,转基因表达,免疫细胞成熟以及疫苗在体外和体内 (小鼠) 的疗效.
比较circRNA LNP与mRNA LNP对抗SARS-CoV-2抗原引起的免疫反应.

主要成果:

通过优化的circRNA LNP平台实现了强大而持久的转基因表达.
在淋巴结排水和强 dendritic 细胞 (DC) 成熟后证明了 circRNA LNP 的大量积累.
与mRNA LNP相比,circRNA LNP疫苗接种诱导了强大的抗体产生,增强了T_h1偏差的细胞反应,以及显著更高的抗原特异性IgG标位.

结论:

优化的circRNA LNP平台促进了有效的circRNA传递给免疫细胞,从而提高了疫苗的疗效.
circRNA LNP代表了对mRNA LNP的有希望的替代品,用于开发下一代针对SARS-CoV-2等传染病的疫苗.

关键词:

这是一个RNARNARNARNARNA.这就是SARS-CoV-2病毒.圆形的RNARNA是一个圆形的RNA.脂质纳米颗粒是一种纳米粒子.疫苗疫苗疫苗疫苗

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