Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression.

Multiplex prime editing creates T cells with defined drug resistance, enabling selective in vivo expansion and rapid pharmacologic suppression in humanized mouse models under immunosuppression.

• Why it matters: Cell and gene therapies need clinically practical ways to turn therapeutic T cells up or down in patients who must keep receiving immunosuppressive drugs.
• What they did: The authors built a multiplex prime-editing platform that edits multiple pathogenic variants in primary human T cells and corrects the HAVCR2 driver mutation in T cells from SPTCL patients, with genomic and transcriptional checks for minimal off-target effects.
• The result: In humanized mouse models, drug-resistant corrected T cells expand selectively under immunosuppressive pressure and remain sensitive to alternative agents, while prime-edited antigen-specific and CAR T cells retain effector function despite pharmacologic immunosuppression.

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