Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.

SLICeVLP enables efficient, high-viability CRISPR editing and pooled loss-of-function/ Perturb-seq screening in primary human macrophages, identifying TNFAIP3 as a central regulator of inflammatory polarization.

• Why it matters: Efficient, scalable gene engineering and pooled screening tools for primary human myeloid cells are limited, constraining functional genomics needed for immunotherapy design.
• What they did: The VLP toolkit delivers CRISPR ribonucleoproteins for knockout, base editing, and epigenetic silencing, and pairs VPX-lentivirus sgRNA delivery with engineered VLP Cas9 protein for SLICeVLP pooled screens in human macrophages.
• The result: Regulators of TNF and CD80 converge on TNFAIP3; TNFAIP3 ablation drives a proinflammatory state resistant to suppressive repolarization and enhances cytotoxicity in chimeric antigen receptor macrophages.

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