Ionizable Coenzyme-Engineered Lipid/Fiber Microplexes Boost Ribosomal Translation to Improve mRNA Therapy for Degenerative Diseases

The study presents a novel approach using ionizable coenzyme Q10 (iCoQ10)-engineered lipid/fiber microplexes (iCLNP@SF) to enhance mRNA therapy for degenerative diseases by restoring the mitochondrial-ribosomal axis. These microplexes improve mitochondrial metabolism and mRNA translation in senescent cells by stabilizing mitochondrial membrane potential, suppressing cGAS-STING activation, and reducing eIF2α phosphorylation. In vivo experiments demonstrated that iCLNP@SF delivery of Gas6 mRNA increased hair follicle density by approximately 50% in an androgenetic alopecia mouse model, and Runx2 mRNA delivery increased new bone formation by about 40% in defect models, outperforming conventional lipid nanoparticles. This strategy shows promise in improving mRNA therapy efficacy for degenerative conditions.