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脂质纳米粒子介导的CRISPR-Cas13a交付用于控制细菌感染

Bookun Kim¹, Hwi Won Seo¹, Kyuri Lee²

¹Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.

Advanced healthcare materials

|November 24, 2024

概括

研究人员开发了新的脂质纳米粒子 (LNP),用于将遗传物质输送到细菌中. 这些LNP显示出对抗细菌感染的前景,通过使治疗剂的向输送成为可能.

科学领域:

生物技术是生物技术.
微生物学微生物学
药物输送系统药物输送系统

背景情况:

脂质纳米颗粒 (LNP) 已被确立用于动物细胞中的核酸输送,特别是在COVID-19疫苗中.
对于细菌,特别是阴性细菌,有效的核酸输送系统仍然在很大程度上未开发.

研究的目的:

选和识别能够将遗传物质输送到细菌中的脂质纳米粒子 (LNP).
评估已识别的LNP在治疗细菌感染的治疗药物的有效性,在体外和体内.

主要方法:

选511个独特的脂质纳米颗粒 (LNPs) 与不同的脂质成分.
使用LNP助手预处理来削弱格兰阴性细菌膜.
优化LNP与DOTAP (10-25mol%) 的组成,以增强等离子体DNA传递.
在LNP中封装一个Cas13a/gRNA表达向量,用于抗菌应用.

主要成果:

两个LNP,LNP 496和LNP 470,证明了对大肠杆菌的高效等离子体输送.
在特定的摩尔比率中加入DOTAP显著改善了LNP介导的等离子体DNA传递.
与LNP封装的Cas13a/gRNA有效控制了临床Escherichia菌株感染在Galleria mellonela和小鼠模型,当与polymyxin B.结合使用时.

结论:

脂质纳米颗粒 (LNP) 代表了向细菌输送核酸的可行平台.
这种基于LNP的输送系统与膜破坏剂相结合,显示出开发针对病原性感染的新型抗菌疗法的潜力.

关键词:

在CRISPR-cas系统中.在Cas13a.其他替代抗生素替代抗生素细菌感染细菌感染脂质纳米颗粒的使用方法核酸的输送核酸的输送

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