From mRNA Vaccines to In Vivo CAR-T Therapy: RNA-LNP Design and the Pharmacology of CAR-Positive Cells

mRNA vaccines established scalable manufacturing and lipid nanoparticle (LNP) delivery for sequence-defined, non-integrating RNA medicines. In vivo CAR-T therapy repurposes this platform to generate CAR-positive lymphocytes after intravenous dosing, but its active product is a time-varying cell population rather than the injected RNA mass. This review critically examines the pharmacological sequence from biodistribution and cell-specific uptake to cytosolic RNA release, surface CAR expression, effector function, and disease response. The evidence comprises primary human T cells, mice, humanized mice, non-human primates, and 11 patients described in one correspondence and two meeting abstracts (as of July 2026). Matched studies show that receptor internalization can outweigh surface abundance, ligand density follows a non-monotonic relationship with delivery, and lipid chemistry and ligand presentation independently alter productive T-cell transfection. Preclinical models demonstrate transient CAR expression and target-cell depletion, whereas current human reports establish feasibility but not durable efficacy, a dose–response relationship, or the incidence of uncommon toxicities. We therefore distinguish administered dose, cell-resolved CAR-positive-cell exposure, and pharmacodynamic response, and propose their joint measurement as the basis for comparing platforms and selecting repeat-dose regimens.