人类T细胞的全基因组CRISPR屏幕揭示了免疫功能的关键调节者
Eric Shifrut1, Julia Carnevale2, Victoria Tobin1
1Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|November 20, 2018
概括
我们开发了一种新的CRISPR选方法, 这种方法确定了调节T细胞反应的关键基因, 这对于癌症免疫治疗和药物发现至关重要.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 人类T细胞对于免疫和癌症免疫治疗至关重要.
- 人类T细胞中的CRISPR查具有挑战性, 但对于目标发现至关重要.
- 鉴定T细胞刺激的调节者是治疗进步的关键.
研究的目的:
- 为人类T细胞开发一种新的CRISPR查方法.
- 确定调节T细胞受体信号传递,增殖和抗癌活性的基因.
- 探索瘤微环境中的免疫抑制媒介.
主要方法:
- 开发了一种称为单指导RNA (sgRNA) 带有Cas9蛋白电穿孔的隐形病毒感染 (SLICE) 的方法.
- 在人类T细胞中进行全基因组功能丧失查.
- 使用SLICE与单细胞RNA测序 (RNA-seq) 结合使用.
主要成果:
- 确定了T细胞受体信号的重要组成部分和增殖的负调节剂.
- 标志着基因干扰增强了癌细胞的死亡.
- 发现了控制对腺信号的基因,
结论:
- 通过SLICE平台,可以在人类T细胞中进行高效的大规模查.
- 通过SLICE,可以为免疫疗法和药物开发提供无偏见的功能基因标.
- 这种方法促进了对T细胞生物学和治疗重编程的理解.
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