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. 2023 Feb 16;1(4):286–303. doi: 10.1038/s44222-023-00030-y

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Fig. 4 — a, mRNA encoding cytokines is packaged in lipid nanoparticles and taken up by cells. The mRNA is then released into the cytosol and translated into cytokines. b, Local cytokine delivery to tumours using lipid nanoparticles encapsulating mRNA-encoding cytokines that locally induce inflammation against the tumour. Systemic mRNA therapy strategies include: harnessing the liver as a production factory to generate re-engineered cytokines, such as an IL-2–albumin fusion protein; treating liver cancer with mRNA encoding pro-inflammatory cytokines; and passively targeting mRNA encoding pro-inflammatory cytokines to the tumour to reshape the tumour microenvironment (TME). Chimeric antigen receptor (CAR) T cells can include a gene to express cytokines, thereby enhancing immune activation. This technique can also be used to engineer other immune cells, for example, genetically engineered myeloid cells, dendritic cells and natural killer cells. These engineered immune cells can modulate the immunosuppressive tumour environment, after systemic adminstration.