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Recently, Ankur Singh et al. reported a nanowire technology that is used to deliver miRNAs to T cells for programming, thereby enhancing anti-tumor efficacy. The research team used cationic polymer-functionalized nanowires to deliver single or multiple microRNAs (miRNAs) to the initial CD8+ T cells without pre-activating the T cells. The cellular programming of the initial T cells can improve the efficacy of adoptive T cell therapy. However, the current in vitro engineering of T cells requires pre-activation of T cells, which causes them to lose their original state. In this study, the authors used functionalized nanowires to program the fate of the initial CD8+ T cells for in vivo therapeutic responses. This was accomplished by delivering single or multiple microRNAs to primary mouse and human CD8+ T cells without pre-activation. The combination of miRNAs delivered through nanowires programmed CD8+ T cells, regulating their adaptability through changes in T cell proliferation, phenotype, and transcriptional regulation, and the secretion of effector molecules. Additionally, the intravenous transfer of engineered mouse CD8+ T cells through nanowire-mediated dual miRNA delivery provided enhanced immune protection against different intracellular pathogens. In vivo analysis showed that simultaneous changes in miR-29 and miR-130 levels in the initial CD8+ T cells reduced the persistence of typical memory T cells while increasing the number of short-lived effector T cells. Nanowires have the potential to be used to regulate CD8+ T cell differentiation and achieve therapeutic responses in vivo without pre-activation.
Original link：https://www.nature.com/articles/s41565-024-01649-7
