通过使用aptamer修饰的聚合物脂质纳米粒子进行核向的CRISPR/Cas传递
Zichen Xu1, Mohammadreza Haghighat2, Niusha Shafiabady3
1School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Ultimo, NSW, 2007, Australia.
Nanomedicine : nanotechnology, biology, and medicine
|March 13, 2026
概括
这项研究开发了胺功能化纳米粒子,以有效地将CRISPR/Cas9输入细胞核. 这种有针对性的方法显著提高了基因编辑效率和乳腺癌细胞增殖抑制.
科学领域:
- 生物技术是生物技术.
- 纳米医学是一种纳米医学.
- 基因治疗 基因治疗
背景情况:
- 对非病毒基因编辑系统来说,有效的CRISPR/Cas核核蛋白 (RNP) 核传递至关重要.
- 目前的非病毒性方法在实现精确有效的核定向传递方面面临挑战.
研究的目的:
- 开发和评估一种新的聚合物-脂质混合纳米粒子系统,用于增强CRISPR/Cas9.9的核传递.
- 用AS1411的aptamer对纳米粒子进行功能化,以向核素并促进核定向的运输.
主要方法:
- 制造AS1411APTAMER功能化的聚合物-脂质混合纳米颗粒.
- 孔焦显微镜用于确认细胞核内的纳米粒子积累.
- 人工智能辅助深层卷积神经网络 (CNN) 用于精确量化纳米粒子和DAPI的同地化.
- 在体外评估CRISPR/Cas9基因淘汰效率和抑制乳腺癌细胞增殖.
主要成果:
- 通过aptamer修饰的纳米粒子在细胞核中成功积累.
- 基于人工智能的分析精确量化了纳米粒子的传递和局部化.
- 使用aptamer功能化的纳米颗粒将GFP阳性细胞减少到30.0% (与非向纳米颗粒的40.8%相比).
- 准Lcn2基因显示出增强的淘汰效果和强大的抑制乳腺癌细胞增殖.
结论:
- 通过aptamer介导的核准显著提高了CRISPR/Cas9编辑效率.
- 这种以核为目标的纳米粒子系统具有推进非病毒基因疗法的潜力.
- 开发的系统为提高基因编辑应用程序的效率和精度提供了一个有希望的策略.
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