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**DFI mRNA** is a preclinical, liver-targeted lipid-nanoparticle mRNA therapeutic comprising modified mRNAs encoding Delta-like ligand 1, Fms-like tyrosine kinase 3 ligand, and interleukin-7. Following transient hepatocyte expression, membrane-bound DLL1 and secreted FLT3-L and IL-7 promote Notch, FLT3, and IL-7 signaling to expand common lymphoid progenitors, improve thymic seeding and de novo thymopoiesis, and restore naïve T-cell output in aged mice. In reported murine studies, DFI mRNA enhanced vaccine-specific cellular and humoral immunity and improved antitumor activity, including responses to immune checkpoint inhibition, without observed autoimmune exacerbation. The program is an early preclinical approach for immunosenescence and age-associated impairment of vaccine and cancer-immunotherapy responses.
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