Genome-Wide CRISPR Screens Map Interferon Regulation in Human Monocytes

Researchers led by Emil Aagaard Thomsen and Jacob Giehm Mikkelsen at Aarhus University, Denmark, published genome-wide CRISPR-Cas9 lentiviral screens in THP-1 human monocytic cells carrying a fluorescent IFNB1 reporter, in Science Signaling (August 18, 2026; coverage by CRISPR Medicine News on August 19). Comparing cells stimulated with cGAMP alone versus cells first primed with IFN-alpha to model an ongoing inflammatory response, the screens identified 356 supporting and 217 restricting genes for cGAS-STING-induced type I interferon expression without priming, and 311 supporting and 177 restricting genes after priming — only 13-14% of which had previously been linked to interferon or STING regulation. The resulting regulatory map links interferon control to autophagy, RNA metabolism, and chromatin modification, implicating TBL1XR1 and HDAC3 in promoting TBK1-mediated signaling via the NCoR/SMRT complex, with potential relevance to tuning immune responses in CRISPR-based gene and cell therapies.