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在癌症中进行有效的CRISPR/Cas9基因组编辑的聚合物微粒纳米粒子

Yuzhen Li¹, Chun Li¹, Jiachang Yan¹

¹School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.

|April 27, 2024

概括

一个新的纳米粒子系统为癌症治疗提供了CRISPR-Cas9基因编辑工具. 这个系统增强了细胞吸收和瘤保留,导致有效的基因沉默和瘤抑制.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
基因治疗基因治疗

背景情况:

克里斯普尔-Cas9基因编辑对癌症治疗具有前景,但需要安全有效的传递系统.
由于安全性和有效性问题,现有的输送方法在临床应用中面临挑战.

研究的目的:

开发和评估一种用于CRISPR-Cas9在癌症中的传递的新型阴离子微粒纳米粒子.
评估纳米粒子在基因组编辑,细胞吸收,生物相容性和体内瘤抑制方面的效率.

主要方法:

使用胆固醇修饰PEI和可生物降解的块共聚合物的纳米粒子系统 (PEG-PC/PEI-CHO/pCas9) 的配方.
与商用脂质体相比,细胞吸收,内体逃逸和转染效率的评估.
使用GFP和Mcl1目标进行体外和体内基因沉默的评估.
在HeLa瘤异种移植小鼠模型中测试瘤抑制功效.

主要成果:

开发的PEG-PC/PEI-CHO/pCas9纳米颗粒证明了细胞吸收和转染效率的提高.
纳米粒子系统显示了改善的生物相容性和体内瘤保留.
在体外和体内都实现了GFP和Mcl1表达的有效下调.
在异种移植模型中观察到显著的瘤抑制和亡诱导.

结论:

PEG-PC/PEI-CHO/pCas9纳米粒子系统为CRISPR-Cas9在癌症中提供有效和安全的平台.
这种方法为在瘤学中推进基因组编辑应用提供了一个有希望的替代方案.

关键词:

细胞灭亡 (apoptosis) 是一种死亡的过程.这就是CRISPR/Cas9的作用.基因编辑基因编辑在Mcl1中.微粒纳米粒子微粒纳米粒子聚碳酸聚碳酸的使用方法

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