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生物模拟金属有机框架的细胞类型特定CRISPR/Cas9传递

Mram Z Alyami¹, Shahad K Alsaiari¹, Yanyan Li²

¹Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center , King Abdullah University of Science and Technology (KAUST) , Thuwal 23955-6900 , Saudi Arabia.

Journal of the American Chemical Society

|January 15, 2020

概括

生物模拟癌细胞膜覆盖的化乳酸框架 (ZIF) 能够针对性地提供CRISPR/Cas9基因编辑工具. 这种方法增强了癌细胞的细胞特异性基因组编辑,

科学领域:

生物医学工程
纳米技术
基因编辑

背景情况:

对于治疗应用而言,有效的和特定于细胞类型的CRISPR/Cas9基因编辑工具至关重要.
目前的交付方法在实现精确的目标和避免非目标效应方面面临挑战.

研究的目的:

开发一个生物模拟平台,用于针对性和细胞特异性的CRISPR/Cas9基因编辑机制.
创建癌细胞膜覆盖的焦化乳酸框架 (ZIFs) 进行增强的传递.

主要方法:

采用CRISPR/Cas9 (CC-ZIF) 装载的化物伊米达酸框架 (ZIF-8) 进行检测.
CC-ZIF被癌细胞膜覆盖,以产生C3-ZIF (细胞膜类型).
在各种细胞系 (MCF-7,HeLa,HDFn,aTC) 和体内评估了细胞吸收和基因组编辑效率.

主要成果:

在癌细胞中,C3- ZIF (MCF) 的吸收率最高,在健康细胞中吸收率微不足道 (HDFn,aTC).
通过C3-ZIF (MCF) 感染,导致MCF-7细胞的EGFP表达被抑制了3倍.
在体内研究证实C3- ZIF (MCF) 在MCF-7瘤中的选择性积累.

结论:

生物模拟C3-ZIF平台可实现高度特定的癌细胞向和基因编辑.
这种方法解决了在进步的基因组编辑技术中对细胞特异性传递的关键需求.
这种策略对未来基因编辑疗法的临床转化具有重大潜力.

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