Macrophage-targeted Mms6 mRNA-lipid nanoparticles promote locomotor functional recovery after traumatic spinal cord injury in mice

• DOI: 10.1126/sciadv.ads2295
• Publication Date: 2025-03-26T18:45:32Z
• Authors: Chunyan Fu; Xiaoqin Jin; Kangfan Ji; Ke Lan; Xingjia Mao; Zhaobo Huang; Jian Chen; Fengdong Zhao; Pengfei Li; Xuefei Hu; Liwen Sun; Ning Lu; Jinjie Zhong; Yingying Chen; Linlin Wang

Traumatic spinal cord injury (SCI) causes severe central nervous system damage. M2 macrophages within the lesion are crucial for SCI recovery. Our previous research revealed that transfected with magnetotactic bacteria–derived Mms6 gene can resist ferroptosis and enhance To address limitations of macrophage transplantation, we developed lipid nanoparticles (LNPs) encapsulating mRNA targeting ( mRNA-PS/LNPs). The efficiency therapeutic effect these LNPs in mice were evaluated. Intravenous administration mRNA-PS/LNPs delivered more mRNAs to lesion-site than those mRNA-LNP group, which resulted enhancing motor function recovery, reducing area scar formation, promoting neuronal survival nerve fiber repair. These effects nullified when depleted. findings suggest macrophage-targeted delivery is a promising strategy repair recovery patients traumatic SCI.