I am a
Home I AM A Search Login

Papers of the Week

Papers: 1 Jul 2023 - 7 Jul 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology

Inflammation/Inflammatory, Musculoskeletal Pain

2023 Jun 02



Therapeutic TNF-alpha Delivery After CRISPR Receptor Modulation in the Intervertebral Disc.


Stover JD, Trone MAR, Weston J, Lewis C, Levis H, Philippi M, Zeidan M, Lawrence B, Bowles RD


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-α has multiple pathways and has been implicated as a primary mediator of disc degeneration. We tested our ability to regulate the multiple TNF-α inflammatory signaling pathways 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-α 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.