一个基于聚胺胺的聚合物纳米粒子平台,用于有效地在体内输送mRNA
Adriano P Pontes1, Steffen van der Wal1, Karin Roelofs1
120Med Therapeutics B.V., Galileiweg 8, 2333 BD Leiden, the Netherlands.
Biomaterials advances
|December 10, 2023
概括
研究人员开发了用于传递信使RNA (mRNA) 的新型生物可降解聚合物纳米粒子. 这些纳米粒子增强基因表达,并显示出新的基于核酸的疫苗和治疗方法的前景.
科学领域:
- 生物技术是生物技术.
- 纳米医学是一种纳米医学.
- 聚合物化学 聚合物化学
背景情况:
- 使者RNA (mRNA) 技术已经迅速发展,特别是在疫苗开发方面.
- 对于治疗应用而言,mRNA的有效和安全输送至关重要.
- 现有的传递系统在传染效率和内体体逃逸方面面临挑战.
研究的目的:
- 开发可生物降解的基于多胺胺的聚合物纳米粒子 (PAA PNPs) 来增强mRNA传递.
- 为了改善内体逃生和mRNA稳定,使用可诺林 (Q) 功能化.
- 为纳米粒子形成创建预先组织的聚合物支架 (ps-PAAQ) 并评估体内性能.
主要方法:
- 聚胺胺) 聚合物的功能化,含有诺基诺林 (Q) 部分.
- 在乙烯基胺核心周围的PAAQ聚合物的共价组合形成ps-PAAQ.
- 将mRNA (EGFP和 luciferase) 加载到ps-PAAQ纳米粒子中.
- 与PEG聚合物涂层共同配制以中和表面电荷.
- 哺乳动物细胞系的体外转染和小鼠体内研究.
主要成果:
- 诺基诺林的结合增强了细胞系中的GFP蛋白质表达.
- 涂有PEG聚合物的纳米颗粒显示出更小的尺寸,中性表面电荷和更好的热稳定性.
- 与未涂层纳米颗粒相比,在体内肌肉内注射带有光酶mRNA的PEG聚合物涂层纳米颗粒显著增加了小鼠的光酶活性.
结论:
- 开发的ps-PAAQ纳米颗粒具有Q和PEG聚合物涂层,代表了mRNA输送的有希望的平台.
- 这项技术提供了改进的传染效率,内体逃生和体内适用性.
- 该平台有潜力开发基于核酸的新型疫苗和治疗各种疾病的疗法.
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