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

László Gál; 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

doi:10.34133/research.0056

Research (Jan 2023)

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

László Gál,
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

Affiliations

László Gál: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Tamás Bellák: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Annamária Marton: National Biotechnology Laboratory, Institute of Genetics, Biological Research Centre, Szeged, Hungary.
Zoltán Fekécs: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Drew Weissman: Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Dénes Török: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Rachana Biju: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Csaba Vizler: National Biotechnology Laboratory, Institute of Genetics, Biological Research Centre, Szeged, Hungary.
Rebeka Kristóf: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Mitchell B. Beattie: Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
Paulo J.C. Lin: Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
Norbert Pardi: Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Antal Nógrádi: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Krisztián Pajer: Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

DOI: https://doi.org/10.34133/research.0056
Journal volume & issue: Vol. 6

Abstract

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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.

Published in Research

ISSN: 2096-5168 (Print); 2639-5274 (Online)
Publisher: American Association for the Advancement of Science (AAAS)
Country of publisher: United States
LCC subjects: Science
Website: https://spj.science.org/journal/research

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