Aptamer-conjugated gold nanoparticles enable selective oligonucleotide delivery into muscle 2 stem cells to promote regeneration of dystrophic muscles

Inefficient targeting of muscle stem cells (MuSCs) represents a major bottleneck of current 27 therapeutic strategies for muscular dystrophies, as it precludes the possibility to promote 28 compensatory regeneration. Here we describe a novel delivery platform, based on gold nanoparticles, 29 that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs 30 conjugation to an aptamer against integrin directs either local or systemic delivery of 31 microRNA-206 to MuSCs, thereby promoting muscle regeneration in a mouse model of Duchenne 32 Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, non33 immunogenic, and adaptable for release of a wide range of therapeutic oligonucleotides into diseased 34 muscles.