| abstract |
Disclosed herein are methods for identifying immunomodulatory genes. In some embodiments, the method comprises of screening a candidate gene comprising: a) expressing an exogenous cellular receptor, or a functional portion thereof, in a plurality of immune cells; b) introducing into said plurality of immune cells: i. a guiding polynucleic acid, or a nucleic acid encoding said guiding polynucleic acid, wherein said guiding polynucleic acid targets said candidate gene; and ii. an exogenous nuclease, or a nucleic acid encoding said exogenous nuclease; thereby generating a plurality of engineered immune cells comprising a genomic disruption in said candidate gene; c) contacting said plurality of engineered immune cells with a plurality of cells expressing a cognate antigen of said exogenous cellular receptor or a functional portion thereof, thereby performing an in vitro assay; and d) determining a readout of said in vitro assay. |