lipid nanoparticle-plasmid micro-dystrophin

lipid nanoparticle-plasmid micro-dystrophin is an experimental non-viral gene therapy designed for the treatment of Duchenne muscular dystrophy (DMD). Developed by researchers at the Sapienza University of Rome, the therapeutic candidate utilizes a microfluidic-formulated lipid nanoparticle (LNP) platform to deliver plasmid DNA encoding micro-dystrophin (μDys) to muscle cells. This approach aims to overcome the limitations of traditional adeno-associated virus (AAV) vectors, such as immunogenicity, high-dose toxicity, and restricted redosing capacity. Preclinical evaluations in mdx4cv-derived dystrophic primary muscle cells and a bioengineered 3D skeletal muscle model (X-MET) have demonstrated that the formulation successfully restores dystrophin expression, improves sarcolemma integrity, reduces fibrosis, and enhances the biomechanical properties of dystrophic tissue.