CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
短发夹 RNA 元件在开发含 shRNA 的 CAR-T 细胞中的评估
英文原题：Evaluation of the Elements of Short Hairpin RNAs in Developing shRNA-Containing CAR T Cells.
查看英文原题
Evaluation of the Elements of Short Hairpin RNAs in Developing shRNA-Containing CAR T Cells.
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中文摘要
短发夹 RNA（shRNA）已成为在多种细胞系统中进行基因敲低的有力工具，包括嵌合抗原受体（CAR）T 细胞。然而，在开发含 shRNA 的 CAR-T 细胞时，哪些 shRNA 元件对其有效性至关重要仍不清楚。在本研究中，我们评估了不同 shRNA 元件对 CAR-T 细胞中靶基因敲低效率的影响，包括启动子强度、方向、多个 shRNA、自我靶向以及正义和反义序列组成。我们的发现强调了在实现有效敲低时考虑多个 shRNA 及其方向的重要性。此外，我们证明使用强启动子和避免自我靶向可以增强 CAR-T 细胞功能。这些结果为合理设计具有 shRNA 介导敲低能力的 CAR-T 细胞提供了框架，这可能会提高基于 CAR-T 细胞的免疫疗法的治疗效果。
展开英文摘要原文
Short hairpin RNAs (shRNAs) have emerged as a powerful tool for gene knockdown in various cellular systems, including chimeric antigen receptor (CAR) T cells.
However, the elements of shRNAs that are crucial for their efficacy in developing shRNA-containing CAR T cells remain unclear. In this study, we evaluated the impact of different shRNA elements, including promoter strength, orientation, multiple shRNAs, self-targeting, and sense and antisense sequence composition on the knockdown efficiency of the target gene in CAR T cells.
Our findings highlight the importance of considering multiple shRNAs and their orientation to achieve effective knockdown.
Moreover, we demonstrate that using a strong promoter and avoiding self-targeting can enhance CAR T cell functionality. These results provide a framework for the rational design of CAR T cells with shRNA-mediated knockdown capabilities, which could improve the therapeutic efficacy of CAR T cell-based immunotherapy.
论文信息
- 作者
- Urak R、Gittins B、Soemardy C、Grepo N、Goldberg L、Maker M、Shevchenko G、Davis A
- 单位
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.United States
- 期刊
- Cancers2023 May 20
- 原文标识
- PubMed 37345185 · DOI 10.3390/cancers15102848
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