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双修饰的穿透蛋白:通过串接和内体逃生域增强核酸输送

Kanako Horikoshi¹, Maho Miyamoto¹, Keisuke Tsuchiya²

¹National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki 210-9501, Japan; Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.

Bioorganic & medicinal chemistry

|August 12, 2024

概括

双变异的细胞透 (CPPs) 具有结合和内体逃生域,显著增强核酸进入细胞的输送. 这种优化提高了潜在的基因治疗应用的细胞内吸收效率.

科学领域:

生物技术是生物技术.
分子生物学分子生物学
药物输送系统药物输送系统

背景情况:

细胞透 (CPPs) 对于核酸等宏分子的细胞内传递至关重要.
优化CPP结构是提高基因传递效率的关键.

研究的目的:

调查双重修改,特别是堆结构和内体体逃生域 (EED) 对CPP有效性的影响.
为了评估增强的细胞吸收的等离子体DNA (pDNA) 复杂的修改CPPs.

主要方法:

合成双修饰的透胺与EED在N-或C-终端和接结构.
修改后的CPPs与pDNA的复合.
评价细胞吸收效率和内细胞分裂途径.

主要成果:

双重修改显著提高了CPP介导的pDNA传递效率.
细胞吸收主要由巨细胞细胞分裂和克拉中介的内细胞分裂介导.
EED的位置 (N或C端) 影响了输送效率.

结论:

结合拼接结构和EED是一个有前途的策略,可以增强CPP介导的核酸输送.
优化的CPP序列对于开发有效的基因传递系统至关重要.
了解吸收机制将为治疗应用的未来CPP设计提供信息.

关键词:

细胞透类.内体体逃生域内体逃生领域核酸输送核酸的交付方式佩内特拉提因 (Penetratin) 是一种透剂.堆结构是指堆的结构.我们的pDNApDNA

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