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.