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脊髓损伤后通过延迟脊髓内递送编码人白细胞介素-10的核苷修饰mRNA恢复运动功能

Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after Spinal Cord Injury.

作者信息

Gál László, Bellák Tamás, Marton Annamária, Fekécs Zoltán, Weissman Drew, Török Dénes, Biju Rachana, Vizler Csaba, Kristóf Rebeka, Beattie Mitchell B, Lin Paulo J C, Pardi Norbert, Nógrádi Antal, Pajer Krisztián

机构信息

Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

National Biotechnology Laboratory, Institute of Genetics, Biological Research Centre, Szeged, Hungary.

出版信息

Research (Wash D C). 2023;6:0056. doi: 10.34133/research.0056. Epub 2023 Mar 9.

DOI:10.34133/research.0056
PMID:36930811
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10013810/
Abstract

Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great challenge. Nucleoside-modified messenger RNA (mRNA) has become a promising new modality that can be utilized for the safe and efficient delivery of therapeutic proteins. Here, we used lipid nanoparticle (LNP)-encapsulated human interleukin-10 (hIL-10)-encoding nucleoside-modified mRNA to induce neuroprotection and functional recovery following rat spinal cord contusion injury. Intralesional administration of hIL-10 mRNA-LNP to rats led to a remarkable reduction of the microglia/macrophage reaction in the injured spinal segment and induced significant functional recovery compared to controls. Furthermore, hIL-10 mRNA treatment induced increased expression in tissue inhibitor of matrix metalloproteinase 1 and ciliary neurotrophic factor levels in the affected spinal segment indicating a time-delayed secondary effect of IL-10 5 d after injection. Our results suggest that treatment with nucleoside-modified mRNAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.

摘要

在体内有效地递送抗炎蛋白以调节受损脊髓的微环境并促进神经保护和功能恢复是一项巨大挑战。核苷修饰的信使核糖核酸（mRNA）已成为一种有前景的新方法，可用于安全有效地递送治疗性蛋白质。在此，我们使用脂质纳米颗粒（LNP）包裹的编码人白细胞介素-10（hIL-10）的核苷修饰mRNA，以诱导大鼠脊髓挫伤性损伤后的神经保护和功能恢复。与对照组相比，向大鼠损伤部位注射hIL-10 mRNA-LNP可显著减少损伤脊髓节段中的小胶质细胞/巨噬细胞反应，并诱导显著的功能恢复。此外，hIL-10 mRNA治疗可诱导损伤脊髓节段中基质金属蛋白酶1组织抑制剂的表达增加以及睫状神经营养因子水平升高，表明注射后5天IL-10具有延迟的二次效应。我们的结果表明，用编码神经保护因子的核苷修饰mRNA进行治疗是脊髓损伤修复的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01ae/10013810/afde6b55e594/research.0056.fig.006.jpg
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3
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