{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T22:00:47Z","timestamp":1781215247509,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,9]]},"group-title":"Neuroscience","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 NS136564-01"],"award-info":[{"award-number":["R01 NS136564-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Trauma to the spinal cord disrupts the blood-spinal cord barrier and triggers a secondary injury cascade characterized by inflammation and progressive neuronal and glial cell death. Therapeutic cytokines and growth factors have shown promise as a treatment in preclinical studies, though their clinical translation is limited by short protein half-lives and the need for invasive intraspinal administration. Lipid nanoparticle-mediated delivery of mRNA offers an alternative strategy that enables transient protein production. Here, we investigated whether intravenously administered mRNA-lipid nanoparticles could leverage the injury-induced disruption of the blood-spinal cord barrier to access the injured spinal cord for local transgene expression. After spinal cord injury in a rat, lipid nanoparticles loaded with reporter mRNA were administered intravenously, and transgene expression was quantified in the spinal cord and peripheral organs. Intravenous delivery within a 6-hours post-injury resulted in local transgene expression in the injured spinal cord, demonstrating that mRNA-lipid nanoparticles cross the disrupted blood-spinal cord barrier. Transgene expression was observed in astrocytes, oligodendrocytes, microglia, and neurons, detected within 3 hours and remained elevated for up to 5 days post-injury. These findings demonstrate that systemic mRNA-lipid nanoparticles delivery exploit transient blood-spinal cord barrier disruption to achieve local gene expression in the injured spinal cord.<\/jats:p>","DOI":"10.64898\/2026.06.04.730155","type":"posted-content","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:15:19Z","timestamp":1781028919000},"source":"Crossref","is-referenced-by-count":0,"title":["Intravenously Delivered Lipid Nanoparticles Access Acute Spinal Cord Injury via Disrupted Vasculature"],"prefix":"10.64898","author":[{"given":"Jacobus","family":"Burger","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Bolstad","sequence":"additional","affiliation":[{"name":"Department of 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