Codelivery of NGFR100W and VEGFA mRNA Enhances Vascular and Neural Repair in Diabetic Peripheral Neuropathy

We aimed to develop a dual-targeted mRNA-based therapy to address both neural degeneration and vascular insufficiency in diabetic peripheral neuropathy. We identified NGFR100W as a mutation that enhances neuritogenic activity without pain sensitization and investigated its transcriptome to explore its ability to uncouple neuroprotective and nociceptive pathways. Combination therapy using lipid nanoparticles for codelivery of NGFR100W and VEGFA mRNA improved blood flow, increased microvessel formation, and preserved nerve function in a diabetic mouse model. This approach, which combines structure-based design and mRNA therapy, offers a novel strategy for decoupling protein functions and developing therapeutic molecules with specific functionalities.