Paul Alexandra R, Al-Jamal Khuloud T
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR.
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Methods Mol Biol. 2025;2965:439-454. doi: 10.1007/978-1-0716-4742-4_22.
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.
选择性蛋白质表达在mRNA治疗中起着至关重要的作用。在本章中，我们提出了一种新型的靶向T细胞的适体药物递送平台，该平台能够将mRNA高效递送至免疫细胞用于免疫治疗。我们概述了适体筛选、适体与mRNA偶联、表征以及转染至T细胞的方案。我们的结果表明，与未靶向的OX40 mRNA相比，与OX40 mRNA偶联的T细胞适体增强了在小鼠离体脾细胞T细胞中的mRNA转染，使CD4+细胞增加了四倍，CD8+细胞增加了七倍。该平台可通过适体筛选针对其他靶点进行定制，有助于开发增强型mRNA疗法。
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