Overview

• Researchers built the first genome-wide CRISPR screening platform optimized for primary human natural killer cells, named PreCiSE.
• Screens pinpointed regulators including MED12, ARIH2 and CCNC whose disruption enhanced both innate and CAR-mediated NK function in preclinical models.
• Edited cells showed improved metabolic fitness, greater pro-inflammatory cytokine production and expansion of cytotoxic subsets under tumor-like suppressive conditions.
• Top hits were validated in vivo across multiple tumor models, with ARIH2 appearing NK-specific and MED12 and CCNC intersecting pathways known from T-cell biology.
• Findings remain preclinical, and the Rezvani team plans further optimization to prioritize edits for translation into next-generation CAR NK products.