有效的交付CRISPR/dCas9-SAM多重基因激活基于半孔二氧化纳米粒子的膀癌治疗
Jinming Xu1, Jiaju Xu1, Chengfang Sun1
1Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
Acta biomaterialia
|March 20, 2025
概括
这项研究开发了用于CRISPR/dCas9-SAM传递的新型纳米粒子,增强了膀癌基因治疗. 该系统精确地准瘤,激活多个基因,并通过提高安全性和效率来抑制癌症生长.
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
- 纳米技术纳米技术
背景情况:
- 膀癌的复杂性需要多基因疗法超出单基因方法.
- 克里斯普尔/dCas9-SAM提供了特定的多重基因激活,但面临着体内传递和病毒载体的安全挑战.
研究的目的:
- 为在膀癌中开发CRISPR/dCas9-SAM基因治疗的安全有效的输送系统.
- 克服病毒载体的局限性,提高向特异性和转染效率.
主要方法:
- 开发了对pH值敏感的空心半孔纳米颗粒 (PLACS NPs),用PLZ4连接体进行修改,以进行向传递.
- 通过使用PLACS NP,同时提供CRISPR/dCas9-SAM组件 (dCas9-VP64,MS2-P65-HSF1,sgRNA).
- 评估了纳米粒子稳定性,等离子体负载,溶酶体逃逸,转染效率和体内抗瘤作用.
主要成果:
- 与Lipofectamine 3000相比,PLACS NPs表现出较高的溶酶体逃逸和转染效率.
- 同时激活四个目标基因抑制了膀癌细胞的增殖和迁移,促进了细胞亡.
- 在体内研究表明,膀瘤生长受阻显著,在瘤部位进行有效的基因编辑和良好的生物安全性.
结论:
- PLACS NPs有效地提供多组件CRISPR/dCas9系统,用于精确的基因编辑和膀癌的抗瘤作用.
- 这种方法克服了体内传递的挑战,为向性膀癌症治疗提供了一个有希望的策略,具有增强的特异性和降低的毒性.
相关概念视频
01:59CRISPR
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
01:28CRISPR/Cas9 Genome Editing
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...