Combined genetic and epigenetic regulation of human primary T cells

An all-RNA CRISPRoff/CRISPRon platform enabled durable epigenetic programming of primary human T cells and could be paired with CAR knock-in to improve preclinical tumor control.

This preclinical cell-engineering study in primary human T cells showed durable multiplexed endogenous gene silencing or activation without sustained CRISPR expression, persistence through cell divisions, stimulations, and in vivo adoptive transfer, and combined Cas12a-dCas9 genetic plus epigenetic engineering that improved CAR-T-mediated in vivo tumor control and survival.

This was platform and preclinical evidence in engineered human T cells and adoptive-transfer tumor models, so it does not establish safety or therapeutic benefit in patients.