{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:51:20Z","timestamp":1791895880220,"version":"4.3.4"},"reference-count":112,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FMBA of Russia","award":["No. 075-15-2025-573"],"award-info":[{"award-number":["No. 075-15-2025-573"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal cord injury (SCI) is a neurological condition often resulting in permanent motor and sensory deficits, for which effective treatments remain limited. RNA interference (RNAi) is a post-transcriptional mechanism of the downregulation of gene expression mediated by small interfering RNAs. RNAi has demonstrated therapeutic efficacy in various neurological disorders, positioning it as a promising yet underexplored therapeutic strategy for SCI. Here, we provide a focused overview of the key pathological processes in SCI, including primary mechanical injury and secondary cascades such as inflammation, mitochondrial dysfunction, excitotoxicity, oxidative stress, multiple forms of cell death, and others. The potential of RNAi to selectively silence genes implicated in these pathological processes, thereby enhancing neuroprotection and functional recovery, is highlighted. We point out that not only protein-coding genes, but non-coding RNAs (ncRNAs) are suitable targets for RNAi. Novel RNAi tools such as CRISPR-Cas13 might revolutionize the field and offer new opportunities for SCI therapy. However, despite all these promising findings, relevant translational studies of RNAi remain scarce. Challenges related to delivery methods, long-term efficacy, and cell-specific targeting must be addressed. Importantly, combining RNAi with other strategies such as cell- or biomaterial-based therapies may enhance therapeutic outcomes. Future investigations should prioritize systematic comparisons of RNAi targets and delivery systems, ideally at single-cell resolution and in different SCI models, to identify the most relevant molecular pathways for clinical translation. Overall, RNAi represents a compelling but still underdeveloped approach for SCI therapy, requiring continued refinement to reach clinical application.<\/jats:p>","DOI":"10.3390\/ijms26209861","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"9861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RNA Interference and Its Key Targets for Spinal Cord Injury Therapy: What Is Known So Far?"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9354-6824","authenticated-orcid":false,"given":"Daria","family":"Chudakova","sequence":"first","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-8633","authenticated-orcid":false,"given":"Vladimir","family":"Kovalev","sequence":"additional","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2936-7029","authenticated-orcid":false,"given":"Matthew","family":"Shkap","sequence":"additional","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Sigal","sequence":"additional","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Biktimirov","sequence":"additional","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alesya","family":"Soboleva","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-4245","authenticated-orcid":false,"given":"Vladimir","family":"Baklaushev","sequence":"additional","affiliation":[{"name":"Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia"},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies, Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"},{"name":"Department of Medical Nanobiotechnology, Medical and Biological Faculty, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/JN.S143236","article-title":"Epidemiology of Worldwide Spinal Cord Injury: A Literature Review","volume":"6","author":"Kang","year":"2017","journal-title":"J. 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