Glycogen nanoparticles for efficient mRNA transduction to T lymphocytes

Abstract T lymphocyte therapies demonstrate significant promise in the treatment of cancer and infectious diseases. An efficient gene delivery system is essential for the safe and reliable introduction of exogenous genes, especially mRNA, into cells to achieve therapeutic purposes. Commercial transfection reagents are suitable for the transduction of plasmids to adherent cells, whereas they are ineffective for suspension cells such as T lymphocytes and for unstable mRNA. Moreover, the cytotoxicity of transfection reagents themselves constitutes an impediment to their application. The challenge of mRNA transduction to T lymphocytes with high efficiency is notably formidable. An innovative transfection strategy is urgently needed. In this study, we synthesized aminated glycogen (AGly) nanoparticles as gene vectors, encapsulating mRNA to facilitate the efficient transfection of T lymphocytes. Compared to commercial transfection reagent polyethylenimine (PEI), the AGly demonstrated favorable biocompatibility. The positive charge provided AGly with pH buffering ability and mRNA-binding capacity. AGly formed stable nanoparticles with mRNA, which were readily internalized by suspension cells and enhanced the cellular uptake of mRNA. In the T lymphocyte model cell lines (Jurkat cells and HuT 78 cells), AGly demonstrated superior transfection efficiency than that of PEI. Consequently, AGly can emerge as a viable mRNA vector for the efficient transfection of T lymphocytes whilst circumventing the issue of cytotoxicity. The AGly designed in this study provides a novel concept for the exploitation of transfection reagents and proposes a promising methodology for the proficient transfection of T lymphocytes which may significantly contribute to the treatment of cancer and other complex diseases.