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

作　　者：LászlóGál Tamás Bellák Annamária Marton Zoltán Fekécs Drew Weissman Dénes Török Rachana Biju Csaba Vizler Rebeka Kristóf Mitchell B.Beattie Paulo J.C.Lin Norbert Pardi Antal Nógrádi Krisztián Pajer 

机构地区：[1]Department of Anatomy,Histology and Embryology,Albert Szent-Györgyi Medical School,University of Szeged,Szeged,Hungary [2]National Biotechnology Laboratory,Institute of Genetics,Biological Research Centre,Szeged,Hungary [3]Institute of Biochemistry,Biological Research Centre,Szeged,Hungary [4]Department of Medicine,University of Pennsylvania,Philadelphia,PA,19104,USA [5]Acuitas Therapeutics,Vancouver,BC,V6T 1Z3,Canada

出　　处：《Research》2023年第4期131-144,共14页研究（英文）

基　　金：N.P.was supported by NIH R01-AI153064.C.V.and A.M.received generous support from the following grants:2020-1.1.6-JÖVŐ2021-00012 and 2022-2.1.1-NL-2022-00008 for the National Biotechnology Laboratory.A.N.was supported by the NKFIH KLINO-117031 grant.

摘　　要：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-105 d after injection.Our results suggest that treatment with nucleoside-modified mRNAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.

关 键 词：protective RESTORATION utilized 

分 类 号：R651.2[医药卫生—外科学]