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Peptide codes for organ-selective mRNA delivery

Nature materials. 2025-09; 
Tie Chang, Yifan Zheng, Mingrui Jiang, Siqi Jia, Jianbo Bai, Zhi Zheng, Shixin Li, Jia Guo, Yue Wang, Yiting Wang, Haixia Liu, Jianlin Liu, Liangyu Ni, Xingdi Cheng, Shuai Liu, Huijuan Zhang, Wei Pi, Feng Lin, Shiyi Liu, Weijian Wang, Guannan Wang, Leyun Wang, Lei Miao, Xueguang Lu, Ziqing Deng, Bing Bai, Zhao Qin, Huajian Gao, Yue Shao
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GenCrispr Cas9 Genome Editing ,Cas9 protein and modified sgRNA (Supplementary Table 17) were purchased from GenScript Get A Quote

摘要

Organ-selective delivery of messenger RNA (mRNA) is critical for fulfilling the therapeutic potential of mRNA-based gene and protein replacement technologies. Despite clinical advances in the hepatic delivery of mRNA using lipid nanoparticles (LNPs), current strategies for extrahepatic-organ-selective mRNA delivery still have limitations. Here we report a peptide-encoded organ-selective targeting (POST) method for the delivery of mRNA to extrahepatic organs after systemic administration, which is based on the modular tuning of LNPs through surface engineering with specific amino acid sequences (POST codes). Molecular dynamics simulations and in vitro and in vivo testing show that the organ-selective targeting o... More

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