Photo‐Enhanced CRISPR/Cas9 System Enables Robust PD‐L1 Gene Disruption in Cancer Cells and Cancer Stem‐Like Cells for Efficient Cancer Immunotherapy,Small

当前位置： X-MOL 学术 › Small › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Photo‐Enhanced CRISPR/Cas9 System Enables Robust PD‐L1 Gene Disruption in Cancer Cells and Cancer Stem‐Like Cells for Efficient Cancer Immunotherapy
Small ( IF 13.0 ) Pub Date : 2020-12-02 , DOI: 10.1002/smll.202004879
Liang Zhao _{1,

2} , Yingli Luo ₁ , Qiaoyi Huang ₁ , Ziyang Cao _{1,

2} , Xianzhu Yang _{1,

3}

Affiliation

Blocking immune checkpoint pathways with an antibody or small interfering RNA (siRNA) has become a promising method to reactivate antitumor responses for cancer treatment. However, both blockade strategies achieve only temporary inhibition of these immune checkpoints. Herein, a photoswitched CRISPR/Cas9 system for genomic disruption of the PD‐L1 gene is developed to achieve permanent blockade of the PD‐1/PD‐L1 pathway; this system is constructed by using a photoactivated self‐degradable polyethyleneimine derivative and the plasmid pX330/sgPD‐L1 (expression of the Cas9 protein and single‐guide RNA targeting PD‐L1). Under light irradiation, this photoswitched CRISPR/Cas9 system efficiently genetically disrupts the PD‐L1 gene in not only bulk cancer cells but also cancer stem‐like cells. As a result, the photoswitched CRISPR/Cas9 system significantly increases the infiltration of CD8⁺ T cells into tumor tissue, leading to effective activation of a T cell‐mediated antitumor response against cancer cells and cancer stem‐like cells. This study provides an alternative strategy to block the PD‐1/PD‐L1 pathway for efficacious immune checkpoint therapy.

中文翻译：

光增强 CRISPR/Cas9 系统可对癌细胞和癌症干细胞样细胞中的 PD-L1 基因进行强力破坏，从而实现有效的癌症免疫治疗

使用抗体或小干扰 RNA (siRNA) 阻断免疫检查点通路已成为重新激活抗肿瘤反应以进行癌症治疗的一种有前途的方法。然而，两种封锁策略只能暂时抑制这些免疫检查点。在此，开发了一种用于PD-L1基因基因组破坏的光开关CRISPR/Cas9系统，以实现PD-1/PD-L1通路的永久阻断；该系统是通过使用光激活自降解聚乙烯亚胺衍生物和质粒 pX330/sgPD-L1（表达 Cas9 蛋白和靶向 PD-L1 的单向导 RNA）构建的。在光照射下，这种光开关 CRISPR/Cas9 系统不仅可以有效地从基因上破坏癌细胞中的 PD-L1 基因，还可以破坏癌症干细胞样细胞中的 PD-L1 基因。因此，光开关 CRISPR/Cas9 系统显着增加了 CD8 ⁺ T 细胞向肿瘤组织的浸润，从而有效激活 T 细胞介导的针对癌细胞和癌症干细胞样细胞的抗肿瘤反应。这项研究提供了另一种阻断 PD-1/PD-L1 通路的策略，以实现有效的免疫检查点治疗。

更新日期：2020-12-28

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11