增强RNA有效载荷和温度稳定性和活动与氧化物纳米颗粒化涂层化
Robert K DeLong1, Juliet Nava-Chavez2, Rakshith Kumar3
1Innovation Development Laboratory, Landmark Bio, 300 North Beacon Street, Watertown, Massachusetts 02472, United States.
ACS pharmacology & translational science
|March 14, 2024
概括
蛋白胺涂层的氧化纳米颗粒稳定RNA,改善疫苗的温度稳定性和有效载荷传递. 这一进步支持基于RNA的治疗方法和疫苗的进一步临床前开发.
科学领域:
- 生物技术是生物技术.
- 材料科学 材料科学 材料科学
- 纳米技术 纳米技术
背景情况:
- 脂质纳米粒子 (LNP) mRNA疫苗面临着低RNA有效载荷和温度稳定性差的挑战.
- 之前的工作成功地应用了胺涂层颗粒用于温度稳定DNA疫苗.
- 氧化纳米颗粒 (ZnO NPs) 正在探索RNA相互作用和传递,重点是稳定.
研究的目的:
- 关于用于RNA稳定和输送的氧化物纳米颗粒的数据.
- 描述这些纳米粒子的物理化学特性和RNA加载效率.
- 为了评估缩在ZnO-protamine纳米颗粒中的RNA的增强温度稳定性和体外功能活性.
主要方法:
- 使用尺寸,泽塔电位和传输电子显微镜对ZnO,ZnO-protamine和ZnO-protamine-RNA纳米粒子进行表征.
- 紫外线光谱用于RNA负载效率评估,用于有效负载量化的RNA化.
- 循环二元化 (CD),微分扫描热量计 (DSC) 和凝电泳用于稳定性分析.
- 在体外mRNA表达和翻译测试中使用各种记者基因和COVID尖端蛋白.
主要成果:
- 高RNA加载效率 (高达95-98%) 通过胺涂层实现.
- 显示了RNA点的显著增加和增强的热稳定性.
- 在各种温度下储存后观察到的RNA完整性和共聚.
- ZnO-protamine-mRNA样本在体外和细胞内保持了高表达活性和功能翻译.
结论:
- 蛋白胺涂层的氧化纳米颗粒有效稳定RNA,增强其热稳定性和有效载荷传递.
- 这些纳米粒子表现出高负载效率,并在热应力后保持功能活性.
- 这些发现支持ZnO-protamine-mRNA的临床前开发,作为基于RNA的疫苗和疗法的一个有前途的平台.
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