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

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, and non-immunogenic, and it can be easily adapted for the release of a wide range of therapeutic oligonucleotides into diseased muscles.
Competing Interests: Competing interests: A patent application has been filed by the Università Cattolica del Sacro Cuore, IMDEA Nanociencias, Inserm and IRCCS Fondazione Santa Lucia with D.P. A.So., J.-J.T., F.M., P.M.-R and A.S. as inventors (Nucleic acid aptamers recognizing the extra cellular domain of alpha7/beta1 integrin dimers and uses thereof. Application number: 102024000007594.). The other authors declare no competing interests.
(© 2025. The Author(s).)