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

The study introduces ionizable coenzyme Q10-engineered lipid/fiber microplexes (iCLNP@SF) as a novel approach to enhance mRNA therapy for degenerative diseases by restoring the mitochondrial-ribosomal axis and boosting ribosomal translation. These microplexes, which replace conventional ionizable lipids with iCoQ10, demonstrated improved mitochondrial metabolism and mRNA translation in senescent cells. In vivo experiments showed 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 traditional lipid nanoparticles. This strategy offers a promising advancement in mRNA therapy efficacy for degenerative conditions.