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脂质纳米粒子通过HITI介导的基因组编辑实现了高效的活体DNA敲进

Jun Hirose¹, Emi Aizawa¹, Shogo Yamamoto¹

¹Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Osaka, Japan.

|January 8, 2025

概括

脂质纳米颗粒可以增强单基因疾病的体内基因组编辑. 使用优化的脂质纳米颗粒实现同质学独立目标集成 (HITI),在小鼠中实现了高效的基因敲击.

科学领域:

分子生物学分子生物学
基因治疗基因治疗
纳米医学是一种纳米医学.

背景情况:

在体内基因组编辑为单一性疾病提供了治疗前景.
有效提供基因组编辑工具是一个关键的挑战.
脂质纳米粒子 (LNP) 是一种潜在的 in vivo 应用的输送系统.

研究的目的:

通过HITI方法研究LNP在体内DNA敲定中的有效性.
为了将HITI与传统的同质导向修复 (HDR) 进行比较,以提高敲进效率.
为了优化LNP交付,在体内进行增强的基因组编辑.

主要方法:

在实验室中对HITI与HDR进行评估,以在肝细胞中的Alb位点进行敲进效率.
优化LNP成分和给药途径以实现体内输送.
在小鼠体内静脉注射LNP封装的基因组编辑组件.
在小鼠肝脏中量化GFP敲门效率.

主要成果:

在实验室中,HITI的敲门效率明显高于HDR.
在小鼠肝脏中通过静脉输入LNP实现了成功的HITI介导的GFP敲门 (2.1-2.7%).
与单次剂量相比,多次静脉注射剂量使肝脏GFP的敲门效率翻了一番 (4.3-7.0%).

结论:

在体内传递基因组编辑组件时,LNP是有效的.
由LNP介导的HITI显示出与HDR相比更高的敲进效率.
优化LNP输送策略,包括重复剂量,可以增强潜在治疗应用的累积基因组编辑效果.

关键词:

基因组编辑基因组编辑同类学独立的有针对性的集成 (HITI)敲进来 - 敲进来脂质纳米粒子 (LNP) 是一种

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