Integrated epigenetic and genetic programming of primary human T cells.

Epigenetic programming in primary human T cells using an all-RNA CRISPR platform enables durable gene regulation without DNA breaks, achieving stable gene silencing or activation.

• Why it matters: This approach addresses safety concerns and limitations of traditional genome editing methods, offering a safer, more controllable way to modify T cell phenotypes for therapies.
• What they did: The researchers developed a multiplexed, all-RNA system employing CRISPRoff and CRISPRon to target and modulate endogenous genes in primary T cells, maintaining effects through cell divisions and in vivo transfer.
• The result: This method enables precise, lasting gene regulation that enhances CAR-T cell efficacy and safety, paving the way for improved cell therapies with reduced genomic risks.