An inherent T cell-activating mRNA delivery carrier for in vivo CAR T generation.

RT-modified oligoethylenimine-based lipid nanoparticles (ERTLNPs) enable ligand-free in vivo mRNA transfection in the spleen and intrinsically activate T cells.

• Why it matters: Scalable, non-invasive in vivo CAR T generation needs mRNA delivery that avoids low lipid-nanoparticle efficiency and the antibody conjugation often required for targeting.
• What they did: Systemic administration of ERTLNPs carrying mRNA preferentially transfected spleen T cells; without exogenous stimulation, the particles triggered T cell activation, mRNA expression, and proliferation.
• The result: ERTLNPs engaged PI3K/AKT/mTOR signalling to reprogram T cell metabolism, restrain exhaustion, and support in situ generation of fibroblast activation protein CAR T cells that eliminated pathological fibroblasts in cancer and fibrosis models with minimal off-target effects.

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