Selective protein expression plays a crucial role in mRNA therapeutics. In this chapter, we present a novel T-cell-targeting aptamer drug delivery platform that enables efficient mRNA delivery to immune cells for immunotherapy. We outline protocols for aptamer selection, aptamer–mRNA conjugation, characterization, and transfection into T-cells. Our results show that the OX40 mRNA-conjugated T-cell aptamer enhances mRNA transfection in murine ex vivo splenocyte T-cells, achieving a fourfold increase in CD4+ cells and a sevenfold increase in CD8+ cells compared to untargeted OX40 mRNA. This platform can be customized for other targets via aptamer selection, facilitating the development of enhanced mRNA therapies.