{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:11:20Z","timestamp":1791648680752,"version":"4.3.4"},"posted":{"date-parts":[[2023,6,2]]},"group-title":"Bioengineering","reference-count":75,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Low back pain (LBP) ranks among the leading causes of disability worldwide and generates a tremendous socioeconomic cost. Disc degeneration, a leading contributor to LBP, can be characterized by the breakdown of the extracellular matrix of the intervertebral disc (IVD), disc height loss, and inflammation. The inflammatory cytokine TNF-\u03b1 has multiple pathways and has been implicated as a primary mediator of disc degeneration. We tested our ability to regulate the multiple TNF-\u03b1 inflammatory signaling pathways\n                  <jats:italic>in vivo<\/jats:italic>\n                  utilizing CRISPR receptor modulation to slow the progression of disc degeneration in rats. Sprague-Dawley rats were treated with CRISPRi-based epigenome-editing therapeutics targeting TNFR1 and showed a decrease in behavioral pain in a disc degeneration model. Surprisingly, while treatment with the vectors alone was therapeutic, TNF-\u03b1 injection itself became therapeutic after TNFR1 modulation. These results suggest direct inflammatory receptor modulation, to harness beneficial inflammatory signaling pathways, as a potent strategy for treating disc degeneration.\n                <\/jats:p>","DOI":"10.1101\/2023.05.31.542947","type":"posted-content","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:45:19Z","timestamp":1685753119000},"source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic TNF-alpha Delivery After CRISPR Receptor Modulation in the Intervertebral Disc"],"prefix":"10.64898","author":[{"given":"Joshua D.","family":"Stover","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A. 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