Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function.

ABSTRACT: Human T cells are central effectors of immunity and cancer immunotherapy. CRISPR-based functional studies in T cells could prioritize novel targets for drug development and improve the design of genetically reprogrammed cell-based therapies. However, large-scale CRISPR screens have been challenging in primary human cells. We developed a new method, single guide RNA (sgRNA) lentiviral infection with Cas9 protein electroporation (SLICE), to identify regulators of stimulation responses in primary human T cells. Genome-wide loss-of-function screens identified essential T cell receptor signaling components and genes that negatively tune proliferation following stimulation. Targeted ablation of individual candidate genes characterized hits and identified perturbations that enhanced cancer cell k

SUBMITTER: Shifrut E 

PROVIDER: S-EPMC6689405 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature