CRISPR-Based Gene Therapy for Type 2 Diabetic Neuropathy

Abstract

Type 2 diabetic neuropathy represents the most prevalent and debilitating chronic complication associated with diabetes mellitus. The condition is fundamentally characterized by a complex interplay of chronic hyperglycemia, lipid metabolism disorders, severe oxidative stress, systemic inflammation, mitochondrial dysfunction, Schwann cell degradation, neurovascular disease, and abnormal insulin signaling pathways. Traditional therapeutic interventions primarily focus on basic blood sugar control, analgesia, neurotrophic therapy, and improving circulation; however, these conventional approaches fail to significantly suppress the underlying neurological damage or reverse disease progression. Emerging as a revolutionary gene-editing tool, CRISPR technology offers unprecedented advantages, including robust targeting capabilities, high programmability, and flexible intervention strategies. These attributes provide highly promising research perspectives for the precise and curative treatment of type 2 diabetic neuropathy. This comprehensive review systematically examines the potential application value of CRISPR technology in managing oxidative stress, inhibiting inflammatory signaling cascades, repairing Schwann cell damage, restoring myelin sheaths, increasing neurotrophic support, correcting metabolic abnormalities, and remodeling neurovascular structures based on the primary pathogenesis of the disease. Furthermore, we critically discuss the current technological bottlenecks hindering clinical translation, specifically focusing on in vivo delivery challenges, in vitro editing and reinfusion limitations, and the complexities of combination therapies. Ultimately, while CRISPR stands as a top-performing technology for the gene therapy of diabetic neuropathies, further critical breakthroughs must be achieved in off-target effect mitigation, accurate delivery mechanisms, long-term safety, and multi-target synergistic control to successfully advance these applications from basic laboratory research to widespread clinical practice.