Engineered zinc finger repressors induce a prolonged and selective repression of SCN9A in nociceptors of nonhuman primates - PubMed
3 hours ago
- #neuropathic pain
- #gene therapy
- #SCN9A
- Engineered zinc finger repressors (ZFRs) target the SCN9A gene, which encodes the Nav1.7 sodium channel involved in neuropathies.
- AAV-mediated ZFR delivery in human iPSC-derived neurons reduced SCN9A without off-target effects.
- In a mouse neuropathic pain model, AAV-ZFR administration led to ≤70% Scn9a repression in DRGs and reduced pain hypersensitivity.
- NHP studies showed SCN9A repression in DRG tissue and nociceptors 1 month post-treatment via AAV9-ZFR IT-lumbar delivery.
- ST-503, a lead AAV9-ZFR product, achieved 50% SCN9A repression in NHPs at 6 months with no dose-limiting toxicity or safety concerns.
- Results support AAV-delivered ZFRs as a potential therapy for peripheral neuropathies.