通过酶和NIR激活的CRISPR/Cas9纳米平台进行时空调节的线粒体基因组编辑
Fei Yang1, Qianqin Ran1, Jiahui Chen1
1Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University Shanghai 200241 China yzxian@chem.ecnu.edu.cn clzhang@chem.ecnu.edu.cn.
Chemical science
|January 26, 2026
概括
研究人员开发了一种双响应的CRISPR/Cas传递平台,用于在瘤中编辑线粒体DNA. 这种纳米平台能够通过精确编辑线粒体DNA来实现向瘤治疗,从而降低瘤细胞的活力.
科学领域:
- 生物医学工程 生物医学工程
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 线粒体DNA (mtDNA) 突变对瘤进展和代谢变化至关重要.
- 在瘤线粒体内进行向基因编辑是很困难的,原因是细胞屏障和缺乏瘤特异激活.
研究的目的:
- 开发一种可控制,双响应的CRISPR/Cas传递平台,用于在瘤中进行时空调节的mtDNA编辑.
- 通过精确的线粒体基因编辑来实现向瘤治疗.
主要方法:
- 设计了一个纳米平台 (UCRP-TPP),集成上转化纳米颗粒 (UCNP),一个APE-1响应的DNA复合体,以及一个线粒体向配体 (TPP).
- 利用内源APE-1酶和外源近红外 (NIR) 光来选择性激活和线粒体释放Cas9/sgRNA.
- 在双重激活时通过CRISPR/Cas系统诱导mtDNA编辑.
主要成果:
- 证明了mtDNA复制数和线粒体膜脱极化的减少.
- 展示了增加的活性氧物种生成和诱导瘤细胞亡.
- 通过体内研究证实了强大的抗瘤疗效.
结论:
- 该UCRP-TPP纳米平台为线粒体基因编辑提供了一种多功能和可控制的策略.
- 这种方法通过利用mtDNA编辑为向瘤治疗提供了一个有希望的途径.
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