The time course of in vivo cellular responses to LNPs

Endogenous trafficking pathways have been demonstrated to be central to the targeting mechanism for clinically approved lipid nanoparticle (LNP) therapies, but cells also actively and transiently respond to intracellular and extracellular environmental pressures. Herein, we characterized the transcriptomic response to LNPs carrying mRNA at different timepoints in vivo. Exposure to LNPs was shown to significantly alter the expression of the endocytosis and lysosome pathways, as well as important signaling pathways.

内源运输通路已被证实是临床获批的脂质纳米颗粒（LNP）疗法靶向机制的核心，但细胞亦会对细胞内与细胞外的环境压力产生主动且瞬时的应答。本研究中，我们对不同时间点下体内携带信使RNA（mRNA）的LNP所引发的转录组响应进行了表征。实验表明，暴露于LNP会显著改变胞吞通路、溶酶体通路以及关键信号通路的基因表达水平。