ArticleJournal of nanobiotechnology2026
A pH‑responsive hydrogel delivering ISOC1 modRNA attenuates disc degeneration by promoting BIRC6‑mediated MYC degradation and inhibiting SBSN expression.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- ROS-responsive biomaterial delivery of the TCM-derived small molecule coptisine protects stem cells and attenuates intervertebral disc degeneration.Frontiers in bioengineering and biotechnology · 2026Article
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Authors and funding
7 authors.
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Abstract
Intervertebral disc degeneration (IDD), a principal cause of chronic low back pain, is characterized by nucleus pulposus cell (NPC) apoptosis and currently lacks effective therapies. Through integrated multi-omics and Mendelian randomization analyses, we identified isochorismatase domain-containing 1 (ISOC1) as a key therapeutic target. To achieve controlled, context-specific expression within the acidic disc microenvironment, we designed an injectable, pH-responsive polyvinyl alcohol-phenylboronic acid-functionalized chitosan (PVA-csPBA) hydrogel for delivery of modified ISOC1 mRNA (modRNA). Mechanistically, ISOC1 promotes BIRC6-mediated ubiquitination and proteasomal degradation of MYC, thereby suppressing its transcriptional target SBSN. Suppression of the MYC/SBSN pathway directly ameliorates lactate-induced mitochondrial dysfunction and apoptosis in NPCs, preserving cellular viability and extracellular matrix homeostasis. In a rat IDD model, localized delivery of PVA-csPBA@ISOC1 modRNA effectively maintained disc hydration, mitigated nucleus pulposus tissue degeneration, and reduced annulus fibrosus fibrosis without observable systemic adverse effects. In summary, this work not only validates ISOC1 as a druggable target and elucidates its protective mechanism via inhibition of the MYC/SBSN pathway, but also establishes pH-responsive hydrogel-based modRNA delivery as a potent and precise regenerative strategy for counteracting IDD progression.
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